DOI: 10.3897/pharmacia.73.e212514

Authors: Elena Arabadzhieva, Atanas Yonkov, Dimitar Bulanov, Georgi Korukov, Zhivko Shavalov, Vanyo Mitev

Abstract: This single-center retrospective observational study included 28 patients with surgical conditions and confirmed COVID-19. The small sample size limited the statistical power to detect a significant reduction in mortality among patients treated with higher-dose colchicine; nevertheless, a trend toward lower mortality was observed. Colchicine treatment was associated with a statistically significant reduction in serum ferritin levels, accompanied by trends toward lower CRP and D-dimer levels. These findings are consistent with the proposed anti-inflammatory effects of colchicine and with previous reports suggesting that earlier administration and higher therapeutic doses may be associated with improved clinical outcomes in patients with COVID-19.

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DOI: 10.3897/pharmacia.73.e204483

Authors: Bozhidar Krastev, Vera Megdanova-Chipeva, Assen Goudev

Abstract: Background: Imatinib is an established first-line treatment for unresectable or metastatic gastrointestinal stromal tumors and is generally regarded as having an acceptable cardiovascular safety profile. Fluid retention, however, is a well-recognized adverse effect, and uncommon cardiovascular complications have also been described during treatment. Results: A 49-year-old woman with gastrointestinal stromal tumor of the small intestine started imatinib at a dose of 800 mg/day after histological and immunohistochemical confirmation of the diagnosis. Two months after treatment initiation, she developed dyspnea, facial and lower-limb edema, and elevated arterial blood pressure. Echocardiography showed preserved left ventricular ejection fraction and preserved global longitudinal strain. A small, hemodynamically insignificant pericardial effusion adjacent to the right atrium was detected during follow-up after initiation of imatinib therapy. NT-proBNP levels became elevated during follow-up and fluctuated over time, whereas troponin values remained low. After treatment with torasemide and candesartan, the patient reported clinical improvement, and the pericardial effusion resolved, although NT-proBNP levels continued to fluctuate over time. Conclusion: The case points to a possible imatinib-associated presentation in which fluid retention, elevated arterial blood pressure, NT-proBNP elevation with subsequent fluctuations, and a small pericardial effusion occurred despite preserved systolic function. It also underlines the value of early cardiological assessment, echocardiographic follow-up with strain imaging, and cardiac biomarkers in patients who develop cardiovascular symptoms during imatinib therapy.

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DOI: 10.3897/pharmacia.73.e188437

Authors: Derar H. Abdel-Qader, Taha Abd-ElSalam Ashraf Taha, Ahmed Khaled Abd-eltawab, Nada K. Abdelsattar, Anas Zakarya Nourelden, Alaa Ahmed Elshanbary, Sarah Makram Elsayed, Moaz Yasser Darwish, Iman Basheti, Sajeda Ghassan Matar

Abstract: Antimicrobial resistance (AMR) is an escalating global health crisis, yet patterns of public understanding and antibiotic consumption in the Middle East and North Africa remain under-researched. This study aimed to evaluate the current landscape of AMR awareness, knowledge gaps, and self-medication practices among the general populations of seven Middle Eastern and North African nations. A large-scale, multicenter, cross-sectional study was conducted involving participants from Egypt, Palestine, Algeria, Sudan, Syria, Libya, and Jordan. Data were collected using an online, self-administered questionnaire and convenience sampling. Knowledge levels were quantified based on responses to standardized questions and categorized as poor, fair, or good. Statistical associations between demographic characteristics and self-medication practices were analyzed using SPSS. A total of 12,729 respondents completed the survey, of whom 74.6% were female. Although awareness was high—with 82.3% recognizing the term “antibiotic resistance”—conceptual understanding was lower. Less than half of the participants correctly identified that antibiotics are ineffective against flu-like viral illnesses. Good knowledge scores were achieved by only 42.6% of the cohort. Among the 28% of participants who reported recent antibiotic use, nearly one-third (29.3%) obtained the medication without a prescription. Demographic analysis revealed that females, urban residents, individuals aged 19–20 years, and those with higher education or medical backgrounds had significantly higher knowledge levels (p < 0.001). Despite widespread recognition of the term “antibiotic resistance,” this study exposes profound gaps in public understanding in the Middle East and North Africa regarding appropriate antibiotic indications and the dangers of self-medication. The disconnect between terminology recognition and actual antibiotic-use behavior highlights an urgent need for targeted, culturally adapted public health campaigns and stricter regulatory enforcement to curb the spread of AMR in the region.

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DOI: 10.3897/pharmacia.73.e204449

Authors: Zana Ibraimi, Andi Haxhiu, Driton Shabani, Vjosana Qeriqi, Adhurim Bresa, Dion Haliti

Abstract: Background: Evidence on community pharmacy professionals’ involvement and preparedness to address opioid misuse and related harm in Kosova remains limited. This study assessed their awareness, attitudes, and self-reported confidence regarding opioid abuse and naloxone use. Methods: A cross-sectional online survey was conducted among 460 community pharmacy professionals across Kosova using a structured online questionnaire. Results: Participants reported high levels of self-reported awareness and generally positive attitudes toward addressing opioid-related problems. Most respondents (93.5%) reported understanding the difference between opioid abuse and misuse, while 75.1% were willing to provide counseling. Familiarity with naloxone was reported by 81.5%, although 43.8% did not feel confident administering it. Confidence in naloxone administration was significantly associated with work experience (p = 0.017). Conclusion: Despite positive attitudes and reported awareness, confidence in naloxone administration was lower, indicating a gap in self-reported preparedness. Practical training and clearer professional and regulatory guidance may help address this gap.

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DOI: 10.3897/pharmacia.73.e215594

Authors: Dzhansu Ilyaz, Eda Altinel, Emanuil Yordanov, Stefka Stoyanova, Kostadin Angelov, Emil Hristov, Stefan Harkov, Valentina Petkova

Abstract: Background: In 1985, at a WHO Conference on the rational use of medicines in Nairobi, Kenya, the problem of “counterfeit medicines” was raised for the first time at the international level. In 2006, amid the ongoing mass influx of counterfeit medicines into markets in Asia, Africa, and developing countries (for example, alarming data from Nigeria show that up to 75% of the market is occupied by counterfeit medicines), the WHO announced the IMPACT initiative (International Medical Products Anti-Counterfeiting Taskforce) as the main tool and approach for WHO’s work against the problem of counterfeit medicines. Until 2006, the EU considered counterfeit medicines to be a problem in developing countries. It was only in 2007 that the EC initiated legislative changes, finalized in Directive 2011/62/EC and Regulation (EU) 2016/161. The cornerstone of this concept is the implementation of a tracking system for prescription medicines. Meanwhile, many countries are ahead of the EU and are implementing their own tracking, serialization, and verification systems; one of these countries is Turkey. Aim: To conduct a comparative analysis of serialization and verification systems between the Republic of Turkey and the EU (Bulgaria, respectively), taking into account the positive and negative aspects of the implemented regulatory regimes. Materials and methods: Analysis of the content of regulatory documents in Turkey and the EU and a systematic review of scientific publications. Results and discussion: The Turkish system is controlled by the state through the medicine agency, whereas in the EU, the system is created and managed on a non-governmental basis. Turkey’s ITS (İlaç Takip Sistemi) was launched in 2009 and is the world’s first fully functional end-to-end system, covering all stakeholders—manufacturers, wholesale distributors, pharmacies, and hospitals. The EU system started in 2019, based on the principle of end-to-end traceability plus an anti-tampering device; it applies mainly to prescription medicines. There are similarities, but also differences, between the two systems. The Turkish system is entirely centralized, state-controlled, and covers all medicines. The European system has elements of decentralization and operates on a non-governmental basis. However, both systems have an irreplaceable role in controlling the availability and accessibility of medicines on the market. Clearly, the Turkish system has more advantages, whereas the European system needs further improvement.

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DOI: 10.3897/pharmacia.73.e211586

Authors: Nisreen Jumaah Jebur, Dheyaa Jabbar Kadhim, Issa Hussein Al Issa

Abstract: Crohn’s disease (CD) is a chronic inflammatory disorder. Ustekinumab (UST) is an effective treatment for CD. Therapeutic drug monitoring (TDM) enhances clinical efficacy while minimizing side effects. This study aimed to evaluate the UST trough level (TL) and anti-drug antibodies (ADAs) and to assess the response of patients with CD to optimize UST treatment. This single-center, cross-sectional study included 76 adult patients with CD receiving maintenance UST for at least 24 weeks. The serum TL of UST and clinical remission were assessed at the same visit, immediately before the next dose. Patients were categorized into two groups: Group A, patients reaching the UST target TL (≥1 µg/mL), and Group B, patients failing to reach it. The association between UST exposure and remission was assessed by binary logistic regression. The remission rate was significantly higher in Group A (78.2%) than in Group B (28.6%) (p < 0.001). Based on the TL of UST, ADA positivity, and disease activity, recommendations were made to continue treatment in 43 patients, escalate therapy or shorten the dosing interval in 20 patients, and switch to another biologic agent in 13 patients. Accordingly, TDM of UST could serve as a valuable approach for optimizing CD therapy.

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DOI: 10.3897/pharmacia.73.e205304

Authors: Yulistiani, Yudistira Nurrizky Grahitaning Putra Rohmaan, Febriansyah N. Utomo, Robby Nurhariansyah, Dinda Monika Nusantara Ratri, Wenny Putri Nilamsari, Desak Made Rendang Dianrana Dewi

Abstract: Persistent pulmonary hypertension of the newborn (PPHN) is a serious neonatal condition characterized by failure of normal pulmonary vascular adaptation after birth, resulting in persistent hypoxemia. In resource-limited settings, limited access to inhaled nitric oxide and extracorporeal membrane oxygenation may increase the use of more accessible pulmonary vasodilators such as oral sildenafil. This study aimed to describe the utilization pattern of oral sildenafil and assess changes in heart rate, respiratory rate, and peripheral oxygen saturation (SpO2) among neonates with PPHN. A retrospective observational study was conducted using electronic medical records of neonates with PPHN who received oral sildenafil between January 2024 and October 2025. Complete cases with documented baseline and final heart rate, respiratory rate, and SpO₂ were included in the paired analysis. Sildenafil dose, dosing frequency, and treatment duration were also evaluated. Changes in clinical parameters were analyzed using paired statistical tests according to the data distribution. A total of 54 neonates were included. Most were term neonates (87.0%) and had a birth weight ≥2,500 g (96.3%). Sildenafil was most commonly administered at a dose of >0.5 mg/kg/dose (63.0%) four times daily (96.3%). Respiratory rate decreased from a mean of 53.44 to 49.63 breaths/minute, with a statistically significant difference (p = 0.008). Heart rate remained stable, changing from 137.28 to 136.87 beats/minute (p = 0.896). SpO₂ increased numerically from 96.37% to 97.26%, but the difference was not statistically significant (p = 0.067). Among neonates with PPHN and complete follow-up documentation, respiratory rate decreased significantly during hospitalization, while heart rate remained stable and SpO₂ showed a nonsignificant numerical increase. However, these observed changes cannot be attributed solely to sildenafil because of the retrospective design, absence of a comparator group, potential selection bias from complete-case analysis, and concurrent supportive therapies. Prospective controlled studies with standardized clinical and echocardiographic assessments are warranted to clarify the role of oral sildenafil in neonatal PPHN management.

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DOI: 10.3897/pharmacia.73.e194149

Authors: Martina Milkovska, Elena Mermeklieva

Abstract: Relevant studies published through April 2026 were identified through searches of PubMed, Web of Science, Scopus, and Google Scholar to summarize the available evidence on objective optical quality assessment. Double-pass technology quantifies retinal image quality using the objective scatter index (OSI), modulation transfer function cutoff frequency, and Strehl ratio. The available evidence demonstrates that elevated OSI values detect early cataract with high sensitivity and specificity and correlate strongly with visual function and surgical outcomes. In myopic eyes, preoperative optical assessment supports surgical planning, with phakic lens implantation generally providing superior optical quality compared with corneal refractive procedures in selected patients. Elevated OSI values in the absence of clinically significant cataract require further evaluation to identify the source of scatter before refractive surgery. Although double-pass technology shows considerable clinical promise, its wider adoption is limited by heterogeneous study designs, protocol variability, and the absence of standardized diagnostic thresholds.

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DOI: 10.3897/pharmacia.73.e194899

Authors: Mario J. Valladares-Garrido, Murillo Cezar Zimmer-Mota, Rodrigo Jesús Amilcar Landaira Romero, Pamela Grados-Espinoza, Ana Paula Mesta-Pintado, Telmo Raúl Aveiro-Róbalo, Danai Valladares-Garrido, Melissa M. Sánchez-Ortiz, Enrique Guillermo Llontop Ynga, Susan M. Oblitas-Guerrero, Víctor Juan Vera-Ponce, Virgilio E. Failoc-Rojas, César Johan Pereira-Victorio

Abstract: An analytical cross-sectional study was conducted among 94 patients with diabetes at Itaugua Hospital, Paraguay. Most participants were women (69.2%), were aged 31–59 years (64.9%), had type 2 diabetes (88.3%), and were receiving treatment (83%). Symptoms of anxiety and depression were observed in 87.6% and 72% of patients, respectively. In the simple regression analysis, depression was positively associated with being divorced (PR: 1.38; 95% CI: 1.13–1.70), whereas having type 2 diabetes was negatively associated with depression (PR: 0.76; 95% CI: 0.60–0.97). Anxiety was positively associated with higher education, being cohabiting or divorced, and receiving diabetes treatment, whereas negative associations were found with age 31–59 years, female sex, type 2 diabetes, and the presence of diabetes-related complications. These findings indicate a high prevalence of mental health problems among patients with diabetes, particularly anxiety and depression, highlighting the influence of sociodemographic and clinical factors.

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DOI: 10.3897/pharmacia.73.e202864

Authors: Jeerisuda Orosram, Rojjares Netthong, Matawee Sakulrak, Anfild Pakprom, Sisira Saengkaeo

Abstract: Self-medication with analgesics is a global public health concern, yet knowledge, attitudes, and behavioral patterns in university populations remain undercharacterized. This cross-sectional study surveyed 423 university students and staff in Thailand using a self-administered questionnaire. Multivariable binary logistic regression was used to identify factors independently associated with inappropriate analgesic use. Inappropriate analgesic use was identified in 79.7% of participants, with analgesic sharing (71.2%), concurrent multi-analgesic use (23.6%), and dose escalation (16.1%) as the most prevalent behaviors. More appropriate attitudes were associated with lower odds of inappropriate analgesic use (aOR 0.919, 95% CI 0.871–0.970), whereas recent analgesic use was associated with higher odds (aOR 2.889, 95% CI 1.485–5.620). Knowledge score was not associated with inappropriate-use classification. Inappropriate analgesic-use behaviors were common and were dominated by medication sharing. Educational strategies focusing solely on factual knowledge may be insufficient, and future medication-safety interventions could address attitudes toward safe use of medications.

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DOI: 10.3897/pharmacia.73.e206262

Authors: Kiril Genov, Yoana Yoncheva, Ventsislava Pencheva, Krassimira Yoncheva, Nevyana Veleva-Krasteva

Abstract: The review focuses on recent achievements regarding the implementation of lipid-based nanoparticles for topical ocular delivery. Lipid-based nanoparticles are very attractive because the carriers themselves provide several advantages. For example, some of the lipid ingredients could increase drug absorption because of their high affinity for cell membranes, whereas other lipid ingredients could function as permeation enhancers. Furthermore, their capacity to provide longer residence time and sustained drug release makes them effective systems capable of overcoming rapid drug elimination via nasolacrimal drainage and tear turnover. The review discusses the advantages and properties of liposomes, cubosomes, and solid lipid nanoparticles in detail. Various examples of the influence of the characteristics of these particles (e.g., mean diameter, surface charge, and structure) on their behavior after topical ocular instillation are included in the respective sections.

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DOI: 10.3897/pharmacia.73.e203882

Authors: Thanatcha Songmuang, Ananya Songmuang, Chonladda Pitchayajittipong, Teeraporn Sadira Supapaan

Abstract: Concurrent use of herbal and conventional medicines increases the risk of significant drug–herb interactions (DHIs). This study aimed to develop and evaluate a curated, severity-stratified DHI alert system integrated into a hospital electronic health record (EHR). A before–after observational study was conducted at a general hospital in Thailand. The team developed an evidence-based DHI database from tertiary references and primary literature. The database was integrated into the Hospital Information for Windows EHR using alert tiers: major, requiring mandatory prescriber confirmation; moderate, requiring clinical rationale; and minor, displayed as a passive notification. During 24 months, 510,910 prescription encounters were recorded, of which 7,278 contained both conventional and herbal medicines. Overall, 544 DHI events were identified. The DHI event rate decreased from 312/239,684 encounters (0.13%) before implementation to 232/271,226 encounters (0.09%) after implementation (p < 0.001). Following implementation, lower DHI co-prescribing rates and increased detection of lower-severity interactions were observed, reflecting improved prescribing safety processes.

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DOI: 10.3897/pharmacia.73.e212118

Authors: Catalina Danila, Lucian Faur, Lucian Mocan, Daniela Simona Cavalu

Abstract: Objectives: The eradication of Helicobacter pylori is often challenged by antimicrobial resistance, adherence issues, and regional variation in treatment outcomes. As a hypothesis-generating step, early-stage pharmaceutical prioritization can identify repurposed or bioactive structures for experimental testing. This study compared the docking profiles of niclosamide and berberine against selected H. pylori enzymatic targets, using levofloxacin as a clinically relevant antibacterial comparator. Materials and methods: Blind molecular docking was performed against H. pylori urease, DNA gyrase subunit A, and shikimate kinase. Top-ranked poses were described using Vina-type scores, three-dimensional binding inspection, two-dimensional residue-interaction mapping, and absorption, distribution, metabolism, excretion, and toxicity (ADMET)/drug-likeness predictions. Docking scores were treated as ranking scores rather than binding free energies or experimental affinity constants. Results: In this small docking matrix, berberine produced the most negative descriptive mean score, while niclosamide produced one of the two top-ranked urease poses. These score differences do not establish differences in binding affinity, target engagement, or biological potency. Levofloxacin was included as a clinically relevant comparator. Predicted ADMET descriptors highlighted compound-specific questions related to exposure, solubility, and formulation but were not interpreted as evidence of therapeutic suitability. Conclusion: The integrated analysis prioritizes niclosamide and berberine for further anti-H. pylori investigation without demonstrating binding, enzyme inhibition, antibacterial activity, or therapeutic efficacy. The predicted poses and scores, considered alongside existing experimental literature and predicted ADMET descriptors, define testable hypotheses for urease inhibition assays, minimum inhibitory concentration (MIC) determination, cytotoxicity testing, and formulation-focused studies.

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DOI: 10.3897/pharmacia.73.e197277

Authors: Martin Donchev, Yanitsa Davidkova, Konstantin Tachkov, Guenka Petrova

Abstract: Background: Older patients with newly diagnosed acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy have poor outcomes, and local pharmacoeconomic evidence from Bulgaria is limited. An exploratory economic model comparing venetoclax plus azacitidine (VEN+AZA) versus azacitidine monotherapy (AZA) was developed using local real-world data. Objective: To estimate the incremental costs, life-years gained (LYG), and quality-adjusted life-years (QALYs) of VEN+AZA versus AZA from the Bulgarian healthcare payer perspective. Methods: A 1-year exploratory state-occupancy model with monthly cycles was developed. Health states were event-free survival (EFS), progressed/relapsed disease (PD/RL), and death. The analysis used local data from 69 patients in total, including 49 patients treated with VEN+AZA and 20 treated with AZA. Overall survival (OS) and reconstructed EFS informed state occupancy. Monthly PD/RL occupancy was derived as the difference between OS and EFS, and death was derived as one minus OS. Direct medical costs included drug acquisition, disease management, hospitalization, monitoring, and supportive and palliative care. QALYs were calculated by applying monthly health-state utility weights. A deterministic tornado diagram and probabilistic Monte Carlo sensitivity analyses were performed. Results: In the base case, VEN+AZA was associated with higher costs and greater health benefits than AZA, with an incremental cost-effectiveness ratio (ICER) of €289,309.59 per QALY and €235,736.28 per LYG. The model estimated higher QALYs and life-years for VEN+AZA, with incremental results driven primarily by improved survival and event-free occupancy. Probabilistic sensitivity analysis revealed that the model was sensitive to changes in efficacy. Conclusion: In this exploratory local-data model, VEN+AZA improved health outcomes compared with AZA at increased cost. The model should be interpreted as hypothesis-generating because of the limited sample size, incomplete progression ascertainment, short time horizon, and use of reconstructed state occupancy.

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DOI: 10.3897/pharmacia.73.e209685

Authors: Susanti Susanti, Aiman Fisabilah, Insan Kamil, Salsabila Adlina, Lina Rahmawati Rizkuloh, Richa Mardianingrum, Marlia Singgih

Abstract: Sargassum polycystum contains phenolic- and flavonoid-reactive constituents, although extraction yield and antioxidant quality may respond differently to processing conditions. This study optimized reflux and maceration extraction using response surface methodology–Box–Behnken design and assessed yield–quality trade-offs. Reflux (50–70 °C, 1–3 h, 1:5–1:15) and maceration (24–72 h, 40–80 mesh, 1:5–1:15) were evaluated in 15-run designs for yield, total phenolic content (TPC), total flavonoid content (TFC), and DPPH IC50. Reflux yielded 5.46–15.38%, whereas maceration yielded 2.01–15.30%. Maceration achieved a higher maximum TPC (62.98 mg GAE/g) and stronger DPPH activity (IC50 = 36.19 µg/mL). Optimal conditions were 50.404 °C, 1.0404 h, and 1:9.55 for reflux and 24 h, 80 mesh, and 1:5.30 for maceration. Reflux favored total recovery, whereas maceration produced phenolic-rich extracts with stronger DPPH activity.

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DOI: 10.3897/pharmacia.73.e199777

Authors: Mervat S. Sammor, Marwan M. Abu-Halaweh, Khadeejha Al Abrouni, Balakumar Chandrasekaran, Adnan Dahadha, Nasha’t Khazaleh

Abstract: In this study, nine derivatives of 3,10-dihydro-2H-1,3-oxazepino[7,6-b]indole (1–9), which combine two bioactive pharmacophoric cores, were synthesized and tested for antibacterial activity against five pathogenic bacterial strains. The resazurin-based microdilution plate method was used to determine minimum inhibitory concentration (MIC) values. Derivative 6 displayed the greatest potency (MIC = 0.0048 mg/mL against S. typhimurium). Molecular docking suggested possible interactions between the ligands and peptidoglycan glycosyltransferases. In silico analysis using SwissADME, ProTox 3.0, Cytotoxicity Predictor Online, quantitative structure–activity relationship (QSAR), and quantitative structure–activity/toxicity (QSAT) modeling suggested high gastrointestinal absorption, adherence to drug-likeness rules, and low predicted cytotoxicity across 198 human cell lines. Toxicological predictions suggested nontoxic behavior of all derivatives, with lower predicted activity in normal fibroblasts than in tumor-derived lines. The findings identify derivative 6 as the most active antibacterial candidate and derivative 5 as a safe lead with balanced antimicrobial potential, supporting further antibacterial drug research and the development of these scaffolds for clinical application.

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DOI: 10.3897/pharmacia.73.e203025

Authors: Olivera Krstic Nakovska, Evgenija Mihajloska, Angjela Debreshlioska, Dimitar Karkinski, Aleksandra Tatabitovska, Aleksandra Grozdanova, Ljubica Shuturkova

Abstract: Respiratory viral infections are major triggers of acute exacerbations of chronic obstructive pulmonary disease, yet they are frequently underdiagnosed using conventional microbiological methods, contributing to empirical antimicrobial prescribing. A prospective observational study was conducted in 70 hospitalized patients to evaluate the integration of multiplex polymerase chain reaction (PCR) diagnostics into a clinical pharmacist-led antimicrobial stewardship program. Respiratory pathogens were identified in 45 patients, with multiplex PCR enabling rapid detection of respiratory viral pathogens not identified by conventional microbiological culture. Following interpretation of the molecular results by the clinical pharmacist, antibiotic discontinuation was recommended in 44 patients, while targeted antimicrobial optimization was performed in nine patients. Human rhinovirus/enterovirus was the only microbiological variable associated with prolonged hospital stay. These findings suggest that improved recognition of viral respiratory infections through rapid molecular diagnostics may support timely therapeutic decision-making and antimicrobial optimization and highlight the potential contribution of clinical pharmacists to antimicrobial stewardship.

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DOI: 10.3897/pharmacia.73.e200063

Authors: Yani Zdravkov, Radomir Dzhambazov, Nevyana Veleva, Vasil Haykin, Alexander Oscar

Abstract: This retrospective study aimed to evaluate the postoperative visual acuity and overall patient satisfaction of three groups of patients who underwent cataract surgery. A total of 56 patients and 67 eyes were evaluated and divided based on the type of intraocular lens (IOL) implanted. The evaluation consisted of examining visual acuity at far and intermediate distances preoperatively and postoperatively. On the 30th postoperative day, contrast sensitivity was evaluated using the Pelli-Robson chart, and all patients completed a questionnaire addressing patient satisfaction at far and intermediate distances, dependence on spectacles, occurrence of halos and glare, and driving difficulties. The present study highlights a clinically relevant intermediate vision advantage of the Evolux™ enhanced monofocal IOL over a standard monofocal IOL while maintaining comparable distance visual acuity and contrast sensitivity. Although extended depth of focus (EDOF) IOLs provided superior intermediate visual acuity, they were associated with lower contrast sensitivity and more frequent photic phenomena in this cohort. The study highlights that enhanced monofocal IOLs may represent a useful compromise between the limited intermediate vision of conventional monofocal lenses and the optical trade-offs associated with EDOF lenses. Larger prospective studies with standardized patient-reported outcome measures and longer follow-up are warranted.

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DOI: 10.3897/pharmacia.73.e206326

Authors: Daniel Argilashki

Abstract: Tamoxifen remains a cornerstone in the treatment of estrogen receptor-positive breast cancer, yet its clinical performance is limited by poor aqueous solubility, high lipophilicity, and interindividual variability associated with CYP2D6-mediated formation of its more potent active metabolites. These challenges necessitate the development of advanced drug delivery systems. Nanotechnology-based formulations, particularly polymeric nanocarriers, have shown potential to improve solubility, pharmacokinetics, and therapeutic efficacy, although they do not inherently overcome CYP2D6-dependent metabolic variability. This review focuses on chitosan and its chemically modified derivatives as promising nanocarriers for tamoxifen delivery. Various modification strategies, including hydrophobic conjugation, graft copolymerization, and surface functionalization, are discussed in relation to encapsulation efficiency, release behavior, and biological performance. Reported studies demonstrate enhanced drug loading, sustained release, improved cellular uptake, and increased anticancer activity. Despite these advances, current research remains limited and lacks systematic comparisons. Further studies are required to optimize formulation design and support clinical translation of chitosan-based systems for tamoxifen therapy.

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DOI: 10.3897/pharmacia.73.e201120

Authors: Aleksina Parvanova, Petya Milushewa, Konstantin Tachkov, Silvia Vandeva, Atanaska Elenkova

Abstract: Introduction: The development of medicine and the introduction of new therapeutic options are leading to increasing scientific attention to rare diseases (RDs) affecting older adults. This requires the application of a systematic approach to drug therapy, with a focus on the identification and management of drug-related problems (DRPs). Objectives: To systematically review the evidence on DRPs in older adults with rare diseases and to evaluate DRPs in a real-world cohort of older patients with acromegaly. Methods: A three-step approach was applied: (1) a systematic review of the literature on DRPs in geriatric patients with RDs; (2) a retrospective study of patients with acromegaly hospitalized at the Expert Center of Rare Endocrine Diseases, University Hospital for Active Treatment in Endocrinology (USHATE) “Acad. Ivan Penchev,” Sofia, Bulgaria, in 2021, with application of the STOPP/START criteria for the assessment of DRPs; and (3) an exploratory analysis of the odds of experiencing a DRP according to the presence of polypharmacy and multimorbidity. Results: A total of six studies met the inclusion criteria in the systematic review. The most common DRPs were associated with therapeutic failure and adverse drug reactions (ADRs), which were inherently serious because they led to hospitalization or death. Based on the retrospective study, a total of 16 DRPs were identified among 42 geriatric patients with acromegaly. Ten potentially inappropriate medications and four cases of prescribing omissions were identified, and a review of the Summary of Product Characteristics revealed two additional DRPs. The variables polypharmacy (OR = 1.3043, p = 0.7701) and multimorbidity (OR = 3.9804, p = 0.3720) were not statistically significant factors for the development of DRPs in the study group. Conclusion: The study identified clinically relevant DRPs and demonstrated the potential value of tools such as the STOPP/START criteria in evaluating therapy in geriatric patients. The results highlight that, despite the severity of DRPs, some of them can be identified and prevented through comprehensive pharmacotherapeutic analysis. This emphasizes the need for more in-depth research on risk factors and long-term follow-up by a clinical pharmacist to optimize pharmacotherapy.

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DOI: 10.3897/pharmacia.73.e194894

Authors: Nurdana Bidan, Ubaidilla Datkhayev, Elmira Serikbayeva, Kairat Zhakipbekov, Galiya Umurzakhova, Azhar Omirbayeva, Zhanar Shimirova

Abstract: Psychiatric disorders significantly impact global health, with treatment-resistant patients facing serious complications. Schizophrenia shows treatment resistance in approximately one-third of cases, while antidepressants are effective in half of users. The rising incidence of suicidal ideation in bipolar disorder necessitates the development of new drugs. This narrative review highlights molecules approved by the FDA and EMA from 2018 onward, detailing new indications and formulations. Key approvals include the antipsychotic lumateperone, drug combinations such as OLZ/SAM and KarXT for schizophrenia and bipolar disorder, and esketamine for treatment-resistant depression. Other notable approvals include brexanolone and zuranolone for postpartum depression. However, no new treatments for anxiety disorders or OCD have been introduced. The findings underscore the importance of ongoing research into new psychiatric medications to enhance efficacy and minimize adverse effects.

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DOI: 10.3897/pharmacia.73.e200443

Authors: Stela Georgieva, Tsvetomil Voyslavov, Christo Chanev, Ognyan Petrov

Abstract: The octanol-water partition coefficient, log Po/w, serves as the standard parameter for hydrophobicity, a property that is correlated with transmembrane distribution, biological activity, and the pharmacokinetic behavior of bioactive compounds. In our investigation, the lipophilic characteristics of thirty-one novel combretastatin A-4 derivatives were evaluated using five chromatographic systems across three reversed-phase high performance liquid chromatography stationary phases. The derived retention factors, log kw, were subsequently correlated with computationally predicted lipophilicity values, clog P. This comparative analysis assessed the congruence between the experimental and theoretical datasets for the analyzed compounds. The relationship between the chemical structure of examined derivatives and their lipophilic characteristics were described. Linear pattern recognition techniques were applied for chemometric analysis.

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DOI: 10.3897/pharmacia.73.e211525

Authors: Khalid A. Alamer, Fawaz M. Alotaibi

Abstract: The Saudi population remains relatively young; however, adults aged 60 years or older represented approximately 6% of the population in 2024 and are expected to reach 14% by 2050. This narrative review describes pharmacist-led deprescribing among older adults in Saudi Arabia. Polypharmacy and potentially inappropriate medications are common, but Saudi evidence remains mainly descriptive. Only one small controlled study has evaluated a deprescribing intervention; most studies examined healthcare professionals’ knowledge, attitudes, and readiness. International studies show that pharmacists can identify inappropriate medications, involve patients and prescribers, and monitor medication withdrawal. However, evidence of improved clinical outcomes remains uncertain. In Saudi Arabia, implementation is challenged by the lack of validated Arabic tools, national guidance, integrated workflows, and defined pharmacist authority. Current healthcare initiatives may support deprescribing, but multicenter intervention studies and standardized national pathways are needed.

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DOI: 10.3897/pharmacia.73.e206275

Authors: Emilio Mateev, Ali Irfan, Stefan Kostov, Muhammed Tilahun Muhammed, Alexander Zlatkov

Abstract: A total of thirty-seven benzofuran derivatives were analyzed as potential monoamine oxidase B (MAO-B) inhibitors using a variety of computational methods, including extra-precision docking, induced-fit docking (IFD), molecular mechanics/generalized Born surface area (MM/GBSA) re-scoring, ChemPLP re-docking, molecular dynamics (MD), and density functional theory (DFT). Docking simulations confirmed that thirteen of the selected compounds showed activity within the MAO-B active site, whereas only three were also bound to MAO-A. Compounds 10 and 16 exhibited the highest ChemPLP fitness scores (161.60 and 159.45, respectively), comparable to the score of the reference drug safinamide. MD simulations implied that the MAO-B/10 complex maintained a stable ligand RMSD value of approximately 0.3 nm, while the MAO-B/16 complex displayed higher fluctuations. Both complexes exhibited similar root mean square fluctuation (RMSF) and radius of gyration (Rg) profiles. Additionally, the electrostatic potentials, the energies of the HOMO and LUMO, the global reactivity indices, and Mulliken atomic charges of 10 and 16 were also calculated through DFT (B3LYP/ 6-311++G(d,p) level of theory). The drug-likeness and the predicted pharmacokinetic properties of the two compounds were additionally evaluated with SwissADME. Based on the conducted in silico study, compounds 10 and 16 emerged as the most promising candidates for further in vitro and in vivo validation.

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DOI: 10.3897/pharmacia.73.e201634

Authors: Dimitar Nikolov, Georgi Nikolov, Lyudmila Kitova, Spas Kitov, Maria-Florance Kitova, Anna A. Mihaylova

Abstract: Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare systemic autoimmune disease characterized by necrotizing inflammation of small blood vessels. Pulmonary–renal syndrome represents one of the most severe clinical manifestations and is associated with high morbidity, rapid progression of renal failure, and increased mortality. Management requires individualized immunosuppressive therapy, careful pharmacological monitoring, and multidisciplinary care. Case presentation: The case of a 54-year-old male with proteinase 3 (PR3)-ANCA-positive vasculitis complicated by rapidly progressive glomerulonephritis, pulmonary infiltrates, and dialysis-dependent acute kidney injury is presented. The initial presentation mimicked severe infection and possible malignancy, which complicated the diagnostic process. Despite induction therapy with corticosteroids and cyclophosphamide, renal recovery was not achieved. Due to refractory disease activity and concerns regarding cumulative cyclophosphamide toxicity, rituximab therapy was initiated. Stabilization of systemic inflammatory activity and regression of pulmonary involvement were subsequently observed, although renal replacement therapy remained necessary. Conclusion: This case highlights the complexity of therapeutic decision-making in severe ANCA-associated pulmonary–renal syndrome. Rituximab represented an effective individualized therapeutic option in a dialysis-dependent patient with refractory disease. Careful pharmaceutical management, infection surveillance, and multidisciplinary monitoring remain essential during biologic immunosuppressive therapy.

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DOI: 10.3897/pharmacia.73.e197960

Authors: Jumanah D. Al-Shawabkeh, Nidal M. F. Abulaban, Ali Ata Alsarhan, Laila Alsawalha, Noor A. Barakat, Rahaf Sarayreh, Sajeda Al-Smadi, Ayat Da’seh

Abstract: Background: Obesity is one of the most significant and prevalent diseases and is associated with multiple risk factors, such as diabetes and hypertension; these risks can be reduced through weight loss. This study aimed to evaluate the perspectives of community pharmacists regarding the dispensing, safety, and efficacy of weight-management medications and to identify knowledge gaps, safe practices, and counseling practices. Methods: A reliability-validated online survey was developed and distributed to community pharmacists in Jordan in 2025. Social media was used to distribute the survey among pharmacists. The survey was used to assess dispensing practices for weight-management medications, knowledge about adverse effects, drug interactions, safe practices, and counseling. Descriptive statistics and inferential analyses were used to analyze the data. Results: A total of 382 community pharmacists participated in the study. Approximately half of the respondents (49.7%) were practicing in Jordan’s central region. The majority of participants were female (70.7%) and held a bachelor’s degree in pharmacy or a Doctor of Pharmacy degree (93%), with a mean age of 32.23 ± 3.44 years. The results showed a notable lack of knowledge regarding the use of medications for weight management, especially the off-label use of newer antidiabetes medications for weight loss. Some pharmacists reported dispensing weight-management medications, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs), sodium-glucose cotransporter-2 (SGLT2) inhibitors, and dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists, without a prescription. Additionally, variations in awareness of the safety considerations, contraindications, and adverse effects of these medications were identified. Furthermore, the study highlighted the importance of pharmacists’ awareness in preventing and managing adverse effects. Conclusion: This study highlights the need for appropriate dispensing and counseling regarding medications used for weight management in obesity to avoid misuse and address knowledge gaps regarding these medications. Targeted educational interventions are recommended to support Jordanian community pharmacists in promoting safe dispensing practices, evidence-based counseling, and improved patient safety.

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DOI: 10.3897/pharmacia.73.e206503

Authors: Antoan Rangelov, Iva Parvova, Emil Hristov, Georgi Momekov, Boris Kadinov, Lyubomir Marinov

Abstract: Tofacitinib has raised cardiovascular safety concerns despite its proven therapeutic value in inflammatory diseases. This study evaluated its preclinical cardiovascular effects in a mouse model after 28 days of treatment with three different doses. Tofacitinib induced dose-dependent reductions in systolic and diastolic blood pressure, with significant effects evident by day 14 and more pronounced by day 28. Heart rate showed only minor, non-significant fluctuations, while serum creatine kinase and creatine kinase-MB decreased. Body weight gain was inhibited in treated animals, and mortality occurred only in the low- and medium-dose groups. The cardiac troponin I assay showed negative results in the control and tofacitinib-treated groups, and an increase in isolated rat basilar artery tone was induced by tofacitinib. Overall, tofacitinib produced measurable cardiovascular and systemic effects, supporting the need for further mechanistic studies and careful cardiovascular risk assessment.

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DOI: 10.3897/pharmacia.73.e196054

Authors: Arviansyah, Sumarno, Edi Mustamsir, Irene Ratridewi, Wisnu Barlianto, Dewi Santosaningsih

Abstract: This exploratory two-stage study combined immunoinformatic screening with ex vivo peripheral blood mononuclear cell (PBMC) stimulation from one 38-year-old man with a mid-deep dermal burn injury involving 35% total body surface area (TBSA) and confirmed methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Upstream candidate selection incorporated S. aureus/MRSA sequence matching and conservation screening against a nonredundant S. aureus pangenome comprising 1,038 GenBank genomes, together with antigenicity, predicted safety, and structural accessibility. Four predicted non-toxic, non-allergenic peptides (A1, A2, B, and H) were tested alone and in combinations for 72 h at 5 µg/mL per peptide using five technical replicate wells per condition. One-way ANOVA with Duncan post hoc testing showed that A2-B-H produced the broadest response profile, including higher CD33+CD38+ (+73%, p < 0.01), CD20+ (+42%, p < 0.01), and IL-4 (+37%, p < 0.01). A1-H yielded the highest CD3+CD16+ (+43%, p < 0.05) and TNF-α (+65%, p < 0.05), whereas A2-H produced the highest total IgG (+31%, p < 0.05). The integrated immunological score ranked A2-B-H highest (16.3/20). These findings support A2-B-H as the leading combination for subsequent functional and translational validation.

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DOI: 10.3897/pharmacia.73.e178613

Authors: Herda Ariyani, Chairun Wiedyaningsih, Raden Ajeng Yayi Suryo Prabandari, Sri Idaiani

Abstract: Depression imposes a substantial global burden, yet poor adherence to antidepressants continues to undermine treatment outcomes. Despite pharmacists’ accessibility, evidence on how their interventions improve adherence remains fragmented and insufficiently synthesized. This scoping review mapped pharmacist-led strategies to enhance antidepressant adherence in depressive disorders. Following PRISMA-ScR and Joanna Briggs Institute guidance, PubMed, Scopus, and Google Scholar were searched for studies published from 2005 to 2025, and 18 eligible studies were identified. Interventions were clustered into educational, behavioral, affective, and provider-targeted approaches. Multicomponent and sustained interventions showed the most consistent improvements in adherence, although effects varied according to intervention intensity and follow-up duration. Key barriers included limited training, workload, and system constraints. This review advances the field by integrating disparate evidence and highlighting the need for standardized, scalable, and culturally responsive pharmacist-led models. These findings inform the optimization of pharmacists’ roles in improving antidepressant adherence, particularly in resource-constrained settings.

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DOI: 10.3897/pharmacia.73.e198079

Authors: Rabab Jameel Hashim, Hiba Najeh Alsaad, Husam Hamza Salman

Abstract: The 1,3,4-oxadiazoles were synthesized by acid-catalyzed condensation of the hydrazides with aromatic aldehydes to give the hydrazones, which were then oxidized to the corresponding 1,3,4-oxadiazoles using I2/K2CO3 in DMSO. Characterization was carried out by FT-IR, 1H NMR, 13C NMR, and EI mass spectrometry. Human oligodendroglioma (HS683) cells and normal human astrocytes (NHA) were used to determine cytotoxicity and the selectivity index (SI). The MTT assay against HS683, using cisplatin as the reference drug, yielded IC50 values lower than the IC50 of cisplatin for all compounds. B2 was the most active compound, with the lowest IC50 (37.71 µg/mL) and the highest SI (14.55). Molecular docking against PI3Kα, CDK2, and FAK suggested possible binding modes for the active compounds. All compounds satisfied Lipinski’s rule of five, were predicted to have high gastrointestinal absorption, and had no predicted P-glycoprotein substrate activity. These results position B2 as a lead compound for further development as an anti-glioma agent.

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DOI: 10.3897/pharmacia.73.e201763

Authors: The Due Ong, Vinh-Quang Tran, Phung Ngoc Minh Nguyen, Hieu Minh Nguyen, Nhat Manh Phan, Bay Van Vo, Thoai Dang Nguyen, Trung Quang Vo

Abstract: Peptic ulcer disease (PUD) imposes a substantial economic burden due to prolonged hospitalization and severe complications. This study evaluated the direct medical costs of inpatient PUD treatment from the healthcare provider perspective in Vietnam. A retrospective study was conducted using the electronic medical records of 1,985 inpatients diagnosed with PUD at a military hospital between 2017 and 2022. Direct medical costs during hospitalization were analyzed using Microsoft Excel 2019 and SPSS version 26.0. The total inpatient treatment cost for PUD during the study period was USD 4,142,121, with a mean cost of USD 2,086.7 per patient. Medication costs amounted to USD 88,640, of which proton pump inhibitors represented the largest proportion (USD 80,350). Medical supplies and prolonged hospitalization were the major contributors to overall expenditures. PUD creates a considerable financial burden on both patients and the healthcare system in Vietnam. Strategies aimed at reducing hospitalization duration and optimizing resource utilization may help decrease treatment costs and improve healthcare efficiency.

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DOI: 10.3897/pharmacia.73.e195725

Authors: Syrym Jiyenbalanov, Assem Kalykova, Kairat Zhakipbekov, Naoko Arakawa, Vitaliy Kamkhen

Abstract: A cross-sectional online survey across all 17 regions of Kazakhstan (n = 385, January–April 2025) assessed occupational burnout among pharmacy professionals using the Maslach Burnout Inventory–Human Services Survey (MBI-HSS). Results showed that 68.8% had high emotional exhaustion, 81.6% had high depersonalization, and 54.3% had reduced personal accomplishment. The composite Burnout Index was 0.56 (IQR 0.50–0.63), above the 0.40 threshold for high burnout. Depersonalization scores were notably higher among males (p < 0.001). The highest burnout scores were observed in the 36–45-year age group and among those with 3–5 years of work experience. Those with secondary pharmaceutical education showed more depersonalization and lower personal accomplishment than bachelor’s graduates (p < 0.05). As the sample skewed toward early-career professionals (71.2% under 25 years of age), these figures most directly characterize early-career pharmacy professionals rather than the workforce as a whole. Situated within the Job Demands–Resources theoretical perspective, these data present region-specific evidence for shaping workforce management approaches in Central Asian pharmacy sectors navigating post-Soviet healthcare reform.

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DOI: 10.3897/pharmacia.73.e212551

Authors: Yozlem Ali Kobakova, Angelina Georgieva Kirkova-Bogdanova, Maria Stamova Vakrilova Becheva, Niya Emilova Semerdzhieva, Stefka Achkova Ivanova, Maria Sevdelinova Chaneva, Ventseslava Petrova Atanasova, Ismail Elhanov Bashov, Yonko Tsvetanov Yonchev, Radoslav Fedeev Todorov, Nikolay Zarkov Bashev, Diana Nikolaeva Teneva, Kamen Valentinov Danov, Maria Georgieva Moneva-Sakelarieva, Kiril Todorov Atliev, Vasil Sotirov Kyosev, Silviya Milchova Pavlova, Petar Yordanov Atanasov

Abstract: This retrospective study evaluates the etiological spectrum, antimicrobial resistance patterns, and pharmacokinetic/pharmacodynamic (PK/PD) challenges in patients with sepsis treated at the Clinic of Internal Diseases, UMBALSM “N. I. Pirogov,” Sofia. A total of 760 blood cultures collected over a 24-month period (12 March 2023–28 February 2025) were analyzed. Sepsis was diagnosed according to Sepsis-3 criteria, including SOFA ≥2 and qSOFA parameters. Positive microbiological growth was identified in 196 samples (25.8%). Patients with positive blood cultures had an average hospital stay of 22 days, while critically ill individuals requiring intubation and ICU transfer stayed for 41 days. Mortality increased sharply in patients aged ≥65 years, with men demonstrating a consistently higher risk across all age groups. The etiological profile was dominated by Staphylococcus spp., followed by Escherichia coli, Klebsiella pneumoniae (including ESBL-producing strains), and Acinetobacter baumannii, highlighting the high prevalence of multidrug-resistant Gram-negative pathogens. Rare isolates such as Providencia stuartii and Citrobacter freundii further demonstrated substantial etiological diversity. Gram-positive isolates exhibited high resistance to macrolides and fluoroquinolones, while susceptibility to vancomycin, teicoplanin, and linezolid remained preserved. Gram-negative organisms–particularly ESBL-producing K. pneumoniae and A. baumannii–showed extensive resistance to beta-lactams and standard cephalosporins. Pharmacokinetic/pharmacodynamic considerations: Sepsis induced significant PK/PD alterations, including an increased volume of distribution for hydrophilic antibiotics; frequent augmented renal clearance (ARC), leading to subtherapeutic exposure; and hypoalbuminemia, which accelerates the clearance of highly protein-bound drugs. These factors necessitate individualized dosing strategies, such as prolonged or continuous beta-lactam infusions, and emphasize the critical role of clinical pharmacists in therapeutic drug monitoring (TDM). Sepsis remains a condition associated with high mortality and substantial therapeutic complexity, intensified by antimicrobial resistance and dynamic PK/PD variability. Optimal management requires early empiric broad-spectrum therapy, followed by precise, individualized dosing tailored to the physiological changes in critically ill patients. Multidisciplinary collaboration between physicians and clinical pharmacists is essential for improving clinical outcomes.

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DOI: 10.3897/pharmacia.73.e199144

Authors: Rawaa M. Hussien, Hanan J. Kassab, Aber Abdul Amir Mohamad

Abstract: Bacterial infections of the anterior segment of the eye remain difficult to manage due to rapid precorneal clearance, limited corneal permeability, and short residence time associated with conventional ophthalmic formulations. These challenges often necessitate frequent dosing, which may reduce patient adherence and therapeutic efficiency. Ofloxacin, a broad-spectrum fluoroquinolone antibiotic, is commonly used for ocular infections; however, its topical effectiveness is limited by poor corneal penetration and low ocular bioavailability. Therefore, this study aimed to develop and characterize ofloxacin-loaded hybrid polymeric nanomicelles based on D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and Poloxamer 188 (P188) and to evaluate their in vitro release profile and ex vivo transcorneal permeation as a strategy to improve the topical ocular delivery potential of ofloxacin. Ofloxacin-loaded nanomicelles were prepared using TPGS and P188 via the thin-film hydration technique. The effect of polymer composition on micellar characteristics, drug encapsulation, release behavior, and corneal permeation was systematically evaluated. The optimized formulation (F8), composed of 30 mg TPGS and 20 mg P188, exhibited a small particle size (14.61 ± 0.06 nm), narrow size distribution (polydispersity index [PDI], 0.158 ± 0.02), mildly negative zeta potential (−6.47 ± 0.4 mV), and high entrapment efficiency (88.7 ± 0.92%). In vitro release studies showed a sustained release profile, with approximately 80% drug release over 10 h, compared with less than 25% from the pure ofloxacin suspension. Ex vivo transcorneal permeation studies using excised sheep cornea demonstrated significantly enhanced drug transport, characterized by increased steady-state flux and reduced lag time. Overall, the findings indicate that hybrid polymeric nanomicelles represent a promising platform for improving the biopharmaceutical performance and corneal transport of topical ofloxacin eye drops. In vivo ocular residence time and clinical antibacterial efficacy were not assessed in this study and should be explored in future investigations. Graphical abstract:

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DOI: 10.3897/pharmacia.73.e205741

Authors: Minh Hoang Le, Quang Dinh Hang, Thanh Binh Trieu, Minh Cuong Nguyen, Quang Vinh Lam, Thai Dien Tran, Minh Chin Huynh

Abstract: Identifying barriers to medication adherence can support the development of targeted interventions designed to improve adherence. This study aimed to identify medication adherence barriers in patients with diabetes, the demographic and health-related factors associated with these barriers, and the relationship between these barriers and the level of medication adherence. This cross-sectional study was conducted among patients with diabetes mellitus receiving outpatient care at three provincial public hospitals in Vietnam between January and March 2026. Exploratory factor analysis identified a three-factor empirical structure of medication adherence barriers, labeled medication management barriers, psychosocial barriers, and motivational barriers. Motivational barriers had the strongest correlation with medication adherence (r = –0.270, p < 0.001). These findings highlight motivational and psychosocial barriers as potential targets for future adherence-improving interventions in diabetes care.

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DOI: 10.3897/pharmacia.73.e198561

Authors: Ma. Danica Ines-Ramil, Christian Angelo R. Rafael, Jimmbeth Zenila P. Fabia, Sheja Ryz Uoiea I. Calamayan, Ruth Valerie S. Dagdagan, Jessica G. Asuncion, Dionisio S. Bucao, Rhian Jaymar D. Ramil

Abstract: Disruption of intestinal barrier integrity contributes to systemic inflammation. This study evaluated the immunomodulatory effects of Lentilactobacillus hilgardii DSB22 isolated from fermented bamboo shoots in a lipopolysaccharide (LPS)-challenged BALB/c murine model. Mice receiving oral administration of L. hilgardii DSB22 for 28 days showed significantly increased intestinal secretory immunoglobulin A (sIgA) levels following LPS challenge. Treatment also reduced tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels and increased interleukin-10 (IL-10) concentrations in serum and spleen homogenates. Histopathological analysis of the distal ileum demonstrated preservation of villus architecture and improved villus height-to-crypt depth ratios in probiotic-treated mice. No significant cytokine changes were observed in non-challenged animals receiving the strain. These findings suggest that L. hilgardii DSB22 exerts immunomodulatory effects and may help protect intestinal barrier integrity during inflammatory conditions.

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DOI: 10.3897/pharmacia.73.e206408

Authors: Yancho Zarev, Rada Nedelcheva, Iliana Ionkova

Abstract: In vitro root cultures (RCs) of Linum alpinum and L. austriacum (Linaceae) were used as model systems to investigate phenylpropanoid pathway regulation and justicidin B (JB) accumulation in response to exogenous vitexin supplementation. JB was quantified by LC-HRESI-MS over a 30-day cultivation period following vitexin treatment at different concentrations and developmental stages. Vitexin exerted species-, concentration-, and stage-dependent effects on JB accumulation. In L. alpinum, vitexin induced a modest increase at 1 μM (1.2-fold), whereas L. austriacum showed a stronger concentration- and cultivation-stage-dependent response. The highest fold increase was observed following treatment with 10 μM vitexin on day 35. The results of this study suggest that exogenous flavonoid supplementation may influence metabolic distribution within the phenylpropanoid network, potentially favoring arylnaphthalene lignan biosynthesis. The study highlights a possible regulatory interaction between flavonoid and lignan pathways in plant in vitro systems.

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DOI: 10.3897/pharmacia.73.e206407

Authors: Yancho Zarev, Rada Nedelcheva, Iliana Ionkova

Abstract: Root cultures (RC) of Linum alpinum and L. austriacum (Linaceae) were investigated for enhanced arylnaphthalene-type lignan production through precursor feeding with coniferyl alcohol (CA). Monitoring the accumulation of justicidin B (JB), as a target metabolite, over a 30-day cultivation period revealed different accumulation profiles in the two species. Both RC were treated with 10, 50, or 100 µM CA on day 25 of cultivation and harvested 5 days later. CA supplementation exerted only a limited effect on JB accumulation in L. alpinum, with the highest level recorded at 100 µM. In contrast, L. austriacum responded more markedly, with 50 µM CA yielding the maximum JB content (1.49 µg/mg DW), representing an approximately twofold increase compared with untreated controls. Further treatment at later cultivation stages confirmed a cultivation-stage-dependent response in L. austriacum and supported 50 µM CA as the most effective precursor-feeding condition. The phytochemical potential, production capacity, and precursor biotransformation capacity of in vitro plant systems are largely governed by the genetic background of the donor species. In addition, in vitro cultures of two related species frequently display marked differences in their metabolic and biosynthetic profiles.

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DOI: 10.3897/pharmacia.73.e204223

Authors: Annette d’Arqom, Heni Sukma Zulfatim, Belinda Anasthasya Tansy, Rimbun, Maulana A. Empitu, Suzita Mohd Noor, Ni Luh Ayu Megasari, Kamolporn Amornsupak

Abstract: Alcoholic liver disease (ALD) is characterized by hepatic steatosis, inflammation, and gut-liver axis dysfunction. Gabapentin, an antiepileptic agent commonly used in the management of alcohol withdrawal syndrome, has demonstrated potential anti-inflammatory properties. This study investigated the effects of gabapentin on alcohol-induced hepatic and intestinal injury using a zebrafish (Danio rerio) model. Adult zebrafish were exposed to 0.5% ethanol for 28 days, followed by gabapentin treatment for 2 or 4 weeks. Liver and intestinal tissues were collected for histopathological evaluation by hematoxylin and eosin staining. Bioinformatic analysis of a publicly available transcriptomic dataset was performed to identify differentially expressed genes associated with alcoholic hepatitis, while interleukin-8 (il8) expression was evaluated using real-time quantitative PCR. Gabapentin treatment was associated with reduced hepatic steatosis and goblet cell hyperplasia during the post-ethanol recovery phase, accompanied by lower il8 expression. These findings provide insight into gut-liver axis dysfunction in ALD and support further investigation of gabapentin as a potential adjunctive therapy for alcohol-associated hepatic and intestinal injury.

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DOI: 10.3897/pharmacia.73.e200360

Authors: Zainab Ali Hussein, Ahmed Hamed Jwaid

Abstract: Oridonin is a natural compound with anti-inflammatory and antioxidant activities; however, its use as a topical therapeutic option for psoriasis has received limited attention. The novelty of this research lies in the design and assessment of topical oridonin ointments and their comprehensive assessment in an imiquimod (IMQ)-induced mouse model of psoriasis-like inflammation through clinical, inflammatory, protein, and gene expression analyses. Thirty-six mice were divided into six groups and treated with paraffin ointment, oridonin ointment (1% or 2%), or mometasone furoate. Oridonin ointments were applied after psoriasis induction. Both formulations of oridonin significantly decreased inflammatory mediators, namely interleukin (IL)-23, IL-17, IL-6, tumor necrosis factor alpha (TNF-α), and nuclear factor kappa B (NF-κB), reduced malondialdehyde (MDA), decreased psoriasis severity, and improved skin thickness. The 2% formulation generally produced greater numerical improvements than the 1% formulation. These findings indicate that oridonin ointment is a promising therapeutic option for psoriasis management through its potent anti-inflammatory impact.

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DOI: 10.3897/pharmacia.73.e194159

Authors: Akram Hasan Kareem, Samer Imad Mohammed, Ahmed Abdali Shihad

Abstract: An observational multicenter cohort study involving 120 patients treated with chemotherapy alone or in combination with pembrolizumab or atezolizumab was conducted. Interleukin-6 (IL-6) levels were measured after six cycles, and response of tumor was estimated with the Response Evaluation Criteria in Solid Tumors (RECIST). Receiver operating characteristic (ROC) analysis was conducted. IL-6 levels were significantly reduced in the chemo-immunotherapy groups compared with the chemotherapy group (p < 0.001). Patients with an objective response had lower IL-6 levels than non-responders (p < 0.001). Post-treatment IL-6 and the neutrophil-to-lymphocyte ratio (NLR) were tested, and both were significant in univariate analysis. However, only post-treatment IL-6 remained independently associated with progressive disease in multivariable analysis. ROC analysis revealed exceptional discriminative performance, with an area under the curve (AUC) of 0.961, 91.6% sensitivity, and 96.0% specificity. Therefore, post-treatment IL-6 was independently associated with disease progression and may demonstrate a promising biomarker for risk stratification in patients with non-small cell lung cancer (NSCLC) and chronic obstructive pulmonary disease (COPD).

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DOI: 10.3897/pharmacia.73.e207442

Authors: Hassan Thoulfikar Alamir, Waleed Khaled Albahadly, Haider F. S. Al-Zubaidy, Ahmed Salih Sahib, Meeqaat H. Altrufi, Najah Hamza

Abstract: Background: Psoriasis is a chronic immune-mediated inflammatory skin disease characterized by excessive keratinocyte proliferation, persistent oxidative stress, and dysregulated inflammatory responses. Increasing evidence suggests that impaired antioxidant defenses and altered NLRP3-associated inflammatory signaling may contribute to psoriasis pathogenesis. Febuxostat, a selective xanthine oxidase inhibitor, has demonstrated antioxidant and anti-inflammatory effects in experimental models of various diseases; however, its potential as a topical treatment for psoriasis has not been investigated. Objective: The present study evaluated the therapeutic effects of topical febuxostat ointment in an imiquimod-induced mouse model of psoriasiform dermatitis and investigated its effects on oxidative stress biomarkers, inflammatory cytokines, and NFE2L2 (NRF2) and NLRP3 mRNA expression. Methods: Psoriasiform dermatitis was induced in BALB/c mice by daily topical application of 5% imiquimod cream. Animals were randomly assigned to the normal control, imiquimod control, clobetasol, and topical febuxostat treatment groups. Disease severity was evaluated using a modified PASI-like scoring system, clinical skin thickness assessment, and histopathological examination. Oxidative stress biomarkers, including malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and nitric oxide (NO), were determined. Tissue concentrations of TNF-α, IL-17A, and IL-23 were quantified by ELISA, while NFE2L2 (NRF2) and NLRP3 mRNA expression levels were assessed using quantitative real-time PCR. Results: Topical febuxostat markedly attenuated imiquimod-induced psoriasiform dermatitis, as evidenced by reduced clinical severity and improvement in histopathological abnormalities, including epidermal hyperplasia and inflammatory cell infiltration. Febuxostat treatment significantly reduced MDA, NO, TNF-α, IL-17A, and IL-23 levels, while increasing SOD activity and GSH levels. Furthermore, febuxostat increased NFE2L2 mRNA expression and reduced NLRP3 mRNA expression, particularly at the 2% concentration. These molecular changes were associated with improved oxidative and inflammatory profiles but did not by themselves establish direct activation of the NRF2 pathway or inhibition of the NLRP3 inflammasome. Conclusion: Topical febuxostat demonstrated significant antipsoriatic effects in the imiquimod-induced mouse model, accompanied by improvements in oxidative stress, inflammatory cytokines, and histopathological abnormalities. The associated changes in NFE2L2 and NLRP3 mRNA expression suggest a potential contribution of altered redox- and inflammation-related gene expression to the observed therapeutic effects. However, protein-level and functional studies are required to determine whether these transcriptional changes translate into direct modulation of the NRF2/NLRP3 signaling pathways. These findings support further investigation of topical febuxostat as a potential nonsteroidal candidate for psoriasis.

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DOI: 10.3897/pharmacia.73.e208292

Authors: Stanislav Georgiev, Lyuboslava Pampulova, Philip Abedinov, Rumen Iliev, Emil Hadzhiev, Dimitar Petkov

Abstract: Pulmonary embolism (PE) is a serious and potentially fatal condition caused by obstruction of the pulmonary arterial system by thrombotic material. While the baseline risk in the general population remains low, it rises significantly in the presence of certain predisposing factors such as major surgery, malignancy, prolonged immobilization, and advanced age (Henke et al. 2020). Corticosteroid therapy increases the risk of venous thromboembolism (VTE) through both direct and indirect mechanisms. Directly, it induces a prothrombotic state by increasing procoagulant factors and suppressing fibrinolysis (Stuijver et al. 2013). Indirectly, long-term glucocorticoid (GCS) therapy causes secondary osteoporosis in 30–50% of patients, resulting in a 160% higher risk of vertebral fractures (Kobza et al. 2021). Major osteoporotic fractures are themselves independent risk factors for VTE (Ventrapragada et al. 2024). Furthermore, these fractures can lead to immobilization. Several underlying diseases and clinical conditions, such as chronic inflammatory diseases, significantly increase the risk of developing PE by promoting hypercoagulability, venous stasis, and endothelial injury, collectively known as Virchow’s triad (Shah et al. 2022). This case report describes a 41-year-old male patient who developed a massive pulmonary embolism shortly after neurosurgical intervention for multiple vertebral fractures. The fractures were associated with long-term corticosteroid therapy for ulcerative colitis. The patient required urgent embolectomy. This case highlights the importance of identifying risk factors associated with an increased incidence of pulmonary embolism, as this enables early detection of postoperative thromboembolic complications and prompt management, ultimately improving outcomes.

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DOI: 10.3897/pharmacia.73.e189397

Authors: Rumina Shaleva, Stefani Danailova, Miroslava Benkova-Petrova, Aleksandar Petrov, Petar Petrov, Svetla Staykova, Polya Nanova

Abstract: Diabetic kidney disease (DKD) remains associated with substantial residual kidney and cardiovascular risk despite renin–angiotensin system blockade and sodium–glucose cotransporter 2 (SGLT2) inhibitor therapy. Routinely collected data from 16 adults with documented DKD who initiated finerenone 10 mg once daily at a single nephrology center were retrospectively analyzed. The primary outcome was the change in urine albumin-to-creatinine ratio (UACR); estimated glomerular filtration rate (eGFR), serum creatinine, serum potassium, and UACR responder rates were secondary outcomes. Measurements were assessed at baseline, 3 months, and 6 months. The mean age was 68.4 ± 9.6 years; 75.0% were women; the median baseline eGFR was 35.6 (interquartile range [IQR] 29.9–56.7) mL/min/1.73 m2; and the median baseline UACR was 57.0 (IQR 19.8–123.3) mg/g. Background angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker therapy and SGLT2 inhibitor therapy were each present in 93.8% of patients. Six-month data were available for 15 patients. Median UACR decreased to 30.0 mg/g at 3 months and 18.0 mg/g at 6 months (Friedman p < 0.001; Kendall’s W = 0.871). Median relative reductions were 28.4% and 54.1%, respectively. At 6 months, 12/15 patients (80.0%) achieved a ≥30% UACR reduction, and 9/15 (60.0%) achieved a ≥50% reduction. No statistically significant longitudinal change was detected in eGFR (p = 0.112) or serum potassium (p = 0.166). A post-baseline potassium value ≥5.5 mmol/L was observed in two patients; no value exceeded 5.5 mmol/L or reached 6.0 mmol/L. In this small uncontrolled cohort, finerenone initiation was associated with a marked reduction in UACR over 6 months. The findings are exploratory and should be interpreted cautiously because of the retrospective design, limited sample size, absence of a comparator, short follow-up, and potential confounding by concomitant therapies.

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DOI: 10.3897/pharmacia.73.e206826

Authors: Lyubomira Radeva, Alejandro Serrano, Maria J. Garrido, Krassimira Yoncheva

Abstract: P60 is a synthetic peptide that binds to forkhead box P3 (FOXP3), inhibiting its activity, and therefore can be implemented in cancer immunotherapies. However, the peptide is characterized by low in vivo stability, poor selectivity, and rapid systemic clearance. Thus, the present study evaluates the possibility of overcoming these limitations by its encapsulation in two types of nanoparticles, specifically chitosan-alginate and chitosan-albumin nanoparticles. The developed nanoparticles possessed optimal physicochemical properties. However, the chitosan-albumin nanoparticles were characterized by higher loading of the peptide. The loading degree of P60 was higher in the chitosan-albumin nanoparticles than in the chitosan-alginate nanoparticles. Faster release in media with a slightly acidic pH was registered for both systems, which was considered an important prerequisite for the selective delivery of the loaded peptide to tumor tissue. In conclusion, both types of the developed biopolymeric nanoparticles can be further evaluated as possible carriers of the peptide.

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DOI: 10.3897/pharmacia.73.e210485

Authors: Margarita Politova, Lilia Karamancheva, Milen Dimitrov, Valentina Petkova

Abstract: Modern pharmaceutical marketing operates at the delicate intersection of business and healthcare. This review systematizes the multifaceted impact of marketing pressure on the rational use of medicines and dietary supplements. It examines the evolution of theoretical marketing frameworks, supplemented by contemporary neuromarketing research on the central nervous system (CNS) and peripheral nervous system (PNS), as well as specific cognitive biases (evaluative conditioning, authority bias, and the fear of missing out [FOMO] phenomenon). Furthermore, the regulatory filters of Directive 2001/83/EC, the Law on Medicinal Products in Human Medicine (LMPHM), and the Food Law (BFSA) are analyzed against four categories of documented social consequences: polypharmacy, erosion of professional trust, cyberchondria, and health inequality. Finally, a dedicated analysis of the pediatric segment highlights the clinical and psychological vulnerabilities of marketing directed at children and parents. In this complex market reality, the strategic role of the pharmacist as the ultimate clinical corrective is highlighted.

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DOI: 10.3897/pharmacia.73.e185850

Authors: Ayuub J. Mohammed, Noor Hatef Naser, Wathiq A. Al-Hachami

Abstract: Tumor-associated carbonic anhydrases (CAs), particularly CA IX and CA XII, are relevant molecular targets because of their role in pH regulation within the tumor microenvironment. In this study, six coumarin-based hydrazide-hydrazone derivatives (AT1–AT6) were designed and synthesized from 6-aminocoumarin through chloroacetamide, ester, and hydrazide intermediates followed by condensation with para-substituted benzaldehydes. The products were obtained in a yield range of 70–95% and characterized by Fourier-transform infrared (FT-IR) and proton nuclear magnetic resonance (1H NMR) spectroscopy. Docking studies were performed against carbonic anhydrase models 2H4N and 7PP9, and the ranking was refined using Prime molecular mechanics/generalized Born surface area (MM-GBSA) analysis. The most favorable MM-GBSA values were observed for AT5 against 2H4N (–46.79 kcal/mol) and AT3 against 7PP9 (–50.56 kcal/mol). QikProp and SwissADME profiling suggested generally acceptable molecular weights, lipophilicity, solubility, and predicted oral absorption. A 200 ns Desmond molecular dynamics simulation of the AT3-2H4N complex showed retention of the modeled binding pose with ligand conformational fluctuations during the trajectory. Overall, these findings identify coumarin-hydrazide-hydrazone derivatives as computationally prioritized scaffolds that require biochemical CA inhibition and cellular validation before any anticancer conclusion can be drawn.

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DOI: 10.3897/pharmacia.73.e189800

Authors: Flora Tkhruni, Svetla Danova, Gayane Melik-Andreasyan, Naira Aleksanyan, Arevik Israyelyan

Abstract: It was shown the comparative antimicrobial activity of postbiotics (bacteriocins and exopolysaccharides) isolated from lactic acid bacteria (LAB) strains of genus Enterococcus and Lactobacillus against three broad panelsof human pathogens. The antimicrobial activity was assessed in a concentration-dependent manner and compared with that of conventional antibiotics. Selected and purified bacteriocins from strains of L. rhamnosus 2012 and E. faecium KE5, for which an MIC of 5 mg/mL was established against S. typhimurium G-38 via the serial dilution method, exhibited the strongest antimicrobial activity across a broad panel of pathogens when tested at this concentration using agar diffusion assays. Postbiotics displayed strain-specific inhibitory effects, highlighting their narrower antimicrobial spectrum relative to antibiotics. It was shown that conventional antibiotics demonstrated broad-spectrum efficacy against susceptible strains but known failures against multidrug-resistant (MDR) isolates. Differences in antimicrobial effects between postbiotics may depend on their interaction with the cell membrane of pathogens. These findings suggest that LAB-derived postbiotics could serve as complementary antimicrobial agents (with antibiotics or another bioactive substance), which may have applications in nutritional and preventive frameworks.

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DOI: 10.3897/pharmacia.73.e208575

Authors: Omaima Ibrahim Saleh, Dheyaa Jabbar Kadhim, Kawthar Faris Nassir

Abstract: Parenteral nutrition (PN) therapy is indicated to meet patients’ nutritional needs when normal feeding is not feasible. This study was designed to explore current practices and barriers to PN from the perspective of pharmacists. Data were collected through semi-structured, face-to-face interviews with pharmacists. The key themes that emerged were knowledge, complications, pharmacists’ roles, and challenges and barriers. The most common educational activities were workshops, board study, undergraduate education, and residency training. The most common complications of PN were fluid and electrolyte abnormalities, infections, and refeeding syndrome. The most common roles of pharmacists were educating patients, calculating PN dosages, monitoring patients, and compounding PN solutions. The most common barriers were shortages of PN components and compounding facilities, inadequate training, and a shortage of experienced staff. In conclusion, this study emphasizes the importance of pharmacists’ roles in PN treatment; however, many barriers make their tasks difficult.

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DOI: 10.3897/pharmacia.73.e188629

Authors: Tonika Stoycheva, Albena Merdzhanova, Katya Peycheva, Veselina Panayotova, Rositsa Stancheva, Neli Markova, Tatyana Hristova, Diana A. Dobreva

Abstract: The present study investigated consumer awareness, consumption patterns, and home cultivation of microgreens in Northeastern Bulgaria using a questionnaire-based survey of 198 adults. Descriptive statistics, exploratory factor analysis (EFA), and K-means cluster analysis were employed to identify patterns of knowledge, familiarity, and consumption behaviour. The results demonstrated high recognition of microgreens as edible plants and general awareness of their nutritional value, including vitamins, minerals, antioxidants, and fibre. However, actual consumption and home cultivation remained relatively limited. Factor and cluster analyses identified three distinct consumer groups differing in nutritional awareness and familiarity with microgreens, which strongly influenced consumption frequency. Despite this relatively high awareness, microgreens are not yet integrated into everyday dietary practices. The findings highlight the need for improved public information, market availability, and practical guidance to support the wider dietary use of microgreens as functional foods.

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DOI: 10.3897/pharmacia.73.e168168

Authors: Tsvetelina Velikova, Maria Kokudeva, Antoaneta Mihova, Adriana Angelova, Blagovesta Pencheva

Abstract: Immune-mediated reproductive failure is increasingly recognized in patients with infertility, particularly those with elevated natural killer (NK) cell activity or other immunological abnormalities. This research note presents clinical experience with immunomodulatory protocols combining Intralipid infusions and low-dose corticosteroids. Intralipid, a soybean oil-based lipid emulsion, is used off-label to downregulate NK cell activity, improve implantation, and enhance pregnancy outcomes, whereas corticosteroids modulate excessive immune responses. The protocols are applied during the preconception period and early pregnancy in selected patients following immunophenotyping of peripheral blood cells. Clinical observations suggest that this combined approach is well tolerated, cost-effective, and potentially beneficial for improving reproductive outcomes in appropriately selected patients with infertility. However, the effectiveness of Intralipid therapy and other therapeutic interventions in reproductive medicine remains controversial, highlighting the need for larger, well-designed randomized controlled trials to clarify their clinical benefits.

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DOI: 10.3897/pharmacia.73.e204786

Authors: Alaa Al-Tarawneh, Wael Abu Dayyih, Derar H. Abdel-Qader

Abstract: The integration of artificial intelligence (AI) into the pharmaceutical sector in Jordan remains limited. This study aimed to measure and analyze changes in pharmacists’ attitudes after the implementation of a targeted educational intervention designed to reduce resistance to AI technology. The study comprised two phases: Phase I, a cross-sectional survey (N = 901), and Phase II, a one-group pretest–posttest design (N = 301). Although 75.1% (n = 677) of the 901 pharmacists reported familiarity with AI, only 41.7% (n = 376) of the total cohort reported actively using AI. The Phase I results identified the factors significantly associated with technology use as graduation after 2020 (adjusted odds ratio [AOR] = 1.943, p < 0.001), having a postgraduate degree (AOR = 2.402, p = 0.002), and the availability of digital infrastructure in the workplace (AOR = 2.099, p = 0.003). The Phase II intervention results showed a significant immediate reduction in the self-reported fear of job replacement (−45.4%), whereas beliefs regarding the need for human oversight remained essentially unchanged (p = 0.324). The digital divide among Jordanian pharmacists may be more strongly associated with technological friction—specifically, a lack of digital infrastructure—than with merely generational resistance. However, further research is needed to determine whether these short-term attitudinal shifts translate into long-term changes in practice.

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DOI: 10.3897/pharmacia.73.e192392

Authors: Delyana Davcheva

Abstract: Aim: Over the past decade, nanomedicine has made significant progress in the development of inorganic nanoparticle (iNP)-based drug delivery systems (DDSs). The aim of this narrative review is to summarize the most recent developments in iNP systems, emphasize their advantages as DDSs, and provide detailed commentary on their impact on human health. A systematic search was performed in the PubMed, Scopus, and Web of Science databases for peer-reviewed original research and review articles published between 2020 and 2025. Relevant scientific data on innovative applications of iNPs in cancer therapy were reviewed. The enormous potential of magnetic nanoparticles (NPs), metal–organic frameworks (MOFs), and iNPs used as carriers of small interfering RNAs (siRNAs) as innovative strategies for enhancing antitumor treatment is highlighted. Conclusion: Continuous progress in research strategies for synthesizing iNPs with optimal properties while minimizing adverse effects on living cells is a prerequisite for even greater translational potential of iNP-based DDSs.

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DOI: 10.3897/pharmacia.73.e197938

Authors: Yousr Talib Sahib Al-Jailawi, Basma Zuheir Al-Metwali, Rafid Hameed Ouj

Abstract: While oral anticoagulants (OACs) are critical for managing thromboembolic diseases, their use carries significant bleeding risks, underscoring the importance of patient comprehension for safety and therapeutic success. Existing tools to measure this knowledge often lack cultural adaptation for Arabic-speaking populations or are restricted solely to vitamin K antagonists. This cross-sectional study aimed to translate, culturally adapt, and psychometrically validate the Oral Anticoagulation Knowledge Tool (AKT) for Arabic-speaking Iraqi patients. The study included 280 adult cardiovascular outpatients in Baghdad (140 prescribed warfarin and 140 prescribed direct oral anticoagulants [DOACs]). Following rigorous forward-backward translation, the adapted tool demonstrated excellent content validity, with a scale content validity index of 0.89, retaining all original items. Principal component analysis confirmed the multidimensional nature of clinical knowledge, extracting eight components from the DOAC cohort and 10 from the warfarin cohort. Educational attainment emerged as the most significant predictor of knowledge scores across both therapeutic modalities (p = 0.003 for DOACs; p = 0.006 for warfarin). The DOAC scale demonstrated acceptable internal consistency (α = 0.700), whereas the full warfarin scale exhibited low overall reliability (α = 0.512), although its specific clinical subdomains showed strong independent reliability (α ranging from 0.695 to 0.972). Ultimately, the Arabic AKT proved to be a culturally congruent and psychometrically sound instrument when used as a domain-specific formative index for identifying knowledge gaps.

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DOI: 10.3897/pharmacia.73.e205995

Authors: Stanislava Kostova, Kristina Belcheva, Nevyana Veleva-Krasteva, Nikolai Dakov

Abstract: The management of ocular hypertension and the various forms of glaucoma during pregnancy and lactation represents a significant clinical challenge. The main concerns are related to the selection of an appropriate therapeutic strategy, with special attention paid to the risks associated with treatment for both the mother and the fetus or breastfed infant. There is no universally accepted management protocol for these patients. Owing to the understandable lack of randomized clinical trials in this population, there is currently no officially approved antiglaucoma medication for use during pregnancy or breastfeeding. Selective laser trabeculoplasty is an excellent option for reducing intraocular pressure during pregnancy and lactation, particularly in view of its favorable safety profile. Two clinical cases of patients with ocular hypertension and elevated intraocular pressure who underwent selective laser trabeculoplasty are presented. A sustained and significant reduction in intraocular pressure was achieved. In both cases, the need for antiglaucoma medication was eliminated throughout the follow-up period.

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DOI: 10.3897/pharmacia.73.e206332

Authors: Elif Ikiz, Muhammed Ahmed-Reda Elosman, Sefika Pinar Senol, Tuba Kara, Bahar Tunctan

Abstract: Objectives: This study investigated the effects of the receptor-interacting serine/threonine-protein kinase 1 (RIPK1) inhibitor necrostatin-1s (Nec-1s) on cardiovascular responses and inflammatory damage in a bilateral hind limb ischemia/reperfusion (I/R) injury model in rats. Methods: The I/R injury model consisted of 3 h of ischemia followed by 24 h of reperfusion. Nec-1s was injected intraperitoneally into the rats 1 h before reperfusion. Results: Nec-1s prevented the hypotensive and tachycardic responses to I/R. The I/R-induced increases in the expression or activity of RIPK1, RIPK3, mixed lineage kinase domain-like pseudokinase, high-mobility group box 1, inhibitor of κB kinase α/β/γ, inhibitor of κBα, nuclear factor-kB p65, inducible nitric oxide synthase, cyclooxygenase-2, and interleukin-1β in cardiac, renal, pulmonary, hepatic, and cerebral tissues, as well as in the serum nitrite and prostaglandin I2 levels of the rats, were prevented by Nec-1s. Nec-1s attenuated the elevation in scores for I/R-induced histopathological changes only in the heart. Conclusion: These findings revealed that Nec-1s prevents the deterioration of cardiovascular responses and inflammatory tissue damage in a hind limb I/R model in rats.

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DOI: 10.3897/pharmacia.73.e199561

Authors: Shahad Sadiq Jafer, Yasir Qasim Almajidi

Abstract: The hyperkeratotic stratum corneum is a principal barrier to the efficient topical treatment of psoriasis and limits drug penetration and therapeutic efficacy. In this regard, the aim of this study was to prepare a new topical delivery system containing clobetasol propionate (CP)-encapsulating nanoliposomes dispersed in Carbopol 940 hydrogel and various plant-derived microneedle-like structures for improved topical drug administration. The optimum formula (F2) had a vesicle size of 100 nm, a low polydispersity index (PDI; 0.152), a moderate zeta potential (−16 mV), and high encapsulation efficiencies of 98.8 ± 0.16% by the indirect method and 94.3 ± 0.49% by the direct method. Physicochemical analyses confirmed that CP was successfully incorporated, ensuring the preservation of structural integrity within the engineered nanoliposomal arrangement. The pH, viscosity, and spreadability of the optimized nanoliposomal hydrogel (F2Hb) were all within suitable ranges for the topical application of nanoliposomes. In vitro drug release studies indicated that the optimum nanoliposomal hydrogel formula (F2Hb) provided a sustained release profile; however, when plant-derived microneedle-like structures were incorporated into the nanoliposomal hydrogel (F2HbM), ex vivo skin deposition improved. In an imiquimod-induced mouse model of psoriasis, F2HbM significantly reduced erythema, scaling, and skin thickness and markedly decreased the levels of interleukin (IL)-17A and IL-23. These results indicated that the nanoliposomal hydrogel was an effective strategy for the topical delivery of CP, with sustained drug release and enhanced skin deposition via microneedle-like structures for the treatment of psoriasis.

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DOI: 10.3897/pharmacia.73.e200901

Authors: Winda Mulyamin, Liong Boy Kurniawan, Andi Alfian Zainuddin, Yanti Leman, Aminuddin Aminuddin, Wimpie Pangkahila, Yulia Yusrini Djabir, Suryani As’ad

Abstract: Background: Central obesity is a condition characterized by increased abdominal adipose tissue and an increased risk of developing cardiometabolic diseases. In subjects with obesity, elevated myeloperoxidase (MPO) levels are observed because of the infiltration of polymorphonuclear leukocytes into adipose tissue, leading to increased oxidative stress. This study aimed to assess the effect of astaxanthin supplementation, a compound with strong antioxidant properties, on serum MPO levels in adult subjects with central obesity. Methods: This study is a quasi-experimental study with an open-label, prospective design. A total of 42 subjects with abdominal obesity participated in the study, including 21 subjects who received 4 mg of astaxanthin supplementation per day for 4 weeks and 21 control subjects who did not receive supplementation. Serum MPO levels were measured using an enzyme-linked immunosorbent assay (ELISA) before and after the intervention. Results: There was a significant difference in MPO levels before and after treatment among subjects with central obesity who received astaxanthin (median 20.30 [16.16] vs. 17.29 [10.23] pg/mL; p = 0.014), whereas there was no difference in MPO levels before and after the study period among subjects in the control group (median 19.94 [7.17] vs. 17.49 [9.14] pg/mL; p = 0.876). Conclusion: Supplementation with 4 mg of astaxanthin for 4 weeks reduces serum MPO levels in adult subjects with central obesity.

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DOI: 10.3897/pharmacia.73.e208174

Authors: Katerina Slavcheva, Yana Gvozdeva, Radiana Staynova, Petya Georgieva, Daniela Grekova

Abstract: Introduction: Red yeast rice (RYR)-containing food supplements (FSs) are widely used. However, considerable variability in their pharmaceutical-technological quality has been reported, highlighting the need for systematic evaluation. Aim: This study aimed to evaluate the pharmaceutical-technological characteristics of RYR-containing FSs and explore possible differences according to the declared formulation composition and dosage form. Materials and methods: A total of 15 commercially available FSs containing RYR were evaluated, including coated and uncoated tablets, as well as hard and soft gelatin capsules. Mass uniformity, mechanical strength, resistance to crushing, friability of uncoated tablets, and disintegration were evaluated according to the requirements of the European Pharmacopoeia (Ph. Eur.), 12th edition. Results: The friability of all uncoated tablets was below 1%, with the lowest value being 0.12%. Mechanical strength ranged from 58.6 to 280 N. The sample with the highest mechanical strength also exhibited the lowest friability and the longest disintegration time. Disintegration times varied from 5 to 40 min and were generally shorter for capsules than for tablets. Two hard gelatin capsule samples failed the mass uniformity test, whereas all four uncoated tablet samples exceeded the pharmacopeial disintegration limits. Discussion: The observed differences may reflect variations in formulation composition and excipient content. Microcrystalline cellulose, polyvinylpyrrolidone, and hypromellose may contribute to mechanical resistance, whereas starch and croscarmellose may promote disintegration. Lipophilic components and plant extracts may also affect dosage-form properties. Conclusion: Some RYR-containing FSs complied with all applicable Ph. Eur. requirements, whereas others showed deviations in mass uniformity or disintegration. The findings demonstrate variability among commercially available products and support the need for systematic pharmaceutical-technological quality assessment.

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DOI: 10.3897/pharmacia.73.e206847

Authors: Nikolay Kalvatchev, Iliya Tsekov, Holly Anna Keogh, Karen Manuelyan

Abstract: Herpes zoster ophthalmicus (HZO) is usually a self-limited condition in which treatment decisions are guided by clinical features. We present a case of a 77-year-old female with HZO following COVID-19 infection and prolonged varicella-zoster virus (VZV) shedding. Despite antiviral therapy and clinical improvement, VZV DNA remained detectable by polymerase chain reaction (PCR) for at least 2 months after symptom onset. The disease had an extended duration, with aberrant lesions beyond the dermatome and residual atrophic scarring. This case raises questions regarding the clinical significance of prolonged viral shedding and the need for widespread vaccination efforts. Moreover, various therapeutic approaches involving different dosages and durations of antiherpetic medications have been adopted despite the lack of established guidelines to support a universal protocol, necessitating careful consideration of clinical and virological monitoring. Nevertheless, further studies are needed to determine whether PCR follow-up may have a role in guiding treatment decisions for herpes zoster.

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DOI: 10.3897/pharmacia.73.e207685

Authors: Gergana Todorova, Tanya Gesheva, Nedyalka Boycheva, Anna Mihaylova

Abstract: Insulin resistance is a central mechanism underlying metabolic syndrome, type 2 diabetes mellitus, obesity, and related cardiometabolic disorders. This narrative review critically evaluates the current evidence regarding vitamin D, berberine, and chromium as complementary nutritional interventions for insulin resistance. A structured literature search was conducted in PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar for English-language publications published between 2010 and March 2026, with landmark earlier studies included where appropriate. Mechanistic, preclinical, observational, and clinical evidence was synthesized narratively. The reviewed supplements influence insulin resistance through distinct mechanisms involving insulin signaling, inflammation, oxidative stress, and glucose metabolism. However, clinical findings remain heterogeneous and appear to depend on baseline nutritional status, metabolic phenotype, supplement formulation, and study design. Current evidence supports their use only as adjuncts to lifestyle modification and evidence-based therapy in selected individuals with increased metabolic risk. Future well-designed randomized controlled trials are required to define their long-term efficacy, safety, and role in personalized metabolic management.

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DOI: 10.3897/pharmacia.73.e201285

Authors: Dina Saleem, Monther Faisal Mahdi, Ayad Mohammed Rasheed

Abstract: Cancer remains a major global health challenge, highlighting the need for novel therapeutic agents with improved selectivity and efficacy. Histone deacetylase (HDAC) inhibition represents an important epigenetic strategy in anticancer drug discovery because it can influence gene expression, cell-cycle regulation, and tumor cell survival. In this computational study, fifteen 4-oxoquinazolin-3(4H)-yl-N-hydroxybenzamide derivatives were evaluated as potential HDAC8-targeting compounds using an integrated in silico workflow. Molecular docking was performed against HDAC8 using the crystal structure deposited under Protein Data Bank (PDB) ID 1T69, with suberoylanilide hydroxamic acid (SAHA) used as the reference inhibitor. The investigated derivatives showed favorable accommodation within the HDAC8 catalytic pocket, with predicted interaction patterns involving zinc coordination, hydrogen bonding, and π-related interactions with key active-site residues. Several derivatives showed favorable predicted docking scores and interaction profiles relative to SAHA, suggesting that the designed quinazolinone–hydroxamate scaffold may be suitable for further prioritization. Prime molecular mechanics generalized Born surface area (MM-GBSA) analysis identified selected derivatives with comparatively favorable calculated binding free-energy contributions, particularly through van der Waals, electrostatic, and lipophilic interactions. In silico absorption, distribution, metabolism, and excretion (ADME) prediction indicated that most derivatives possessed acceptable drug-like and pharmacokinetic descriptors, including physicochemical properties, predicted oral absorption, and limited central nervous system (CNS) activity. Density functional theory (DFT) analysis provided supportive electronic-level information by identifying molecular regions that may contribute to hydrogen bonding and zinc coordination. A 100 ns molecular dynamics simulation of the HDAC8–derivative 15 complex suggested the short-timescale persistence of one representative predicted binding pose under the selected simulation conditions. Overall, this study identifies selected 4-oxoquinazoline hydroxamic acid derivatives as preliminary computational leads for further experimental validation as potential HDAC8-targeting compounds.

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DOI: 10.3897/pharmacia.73.e205720

Authors: Baraa Mahmood Shihab, Yasir Qasim Almajidi

Abstract: Diabetic ulcers are a leading cause of lower-extremity amputations, with wound infection being the chief cause of therapeutic failure. Traditional topical dressings fail to maintain effective antibiotic concentrations at the wound site over prolonged periods and cannot eliminate biofilm-embedded organisms. A thermoresponsive injectable in situ gel containing levofloxacin hemihydrate-loaded poly(lactic-co-glycolic acid) nanoparticles, with or without hyaluronic acid, was developed for the local treatment of infected diabetic ulcers. The optimized nanoparticles had a size of 77.1 nm, a zeta potential of +55.90 mV, a polydispersity index of 0.240, and an encapsulation efficiency of 98.6%. The incorporated gels exhibited a sol–gel transition at 32.1–34.6 °C, with suitable viscosity and syringeability, and released levofloxacin for 240 h in formulas A and A+ and for 336 h in formula B, in accordance with the Korsmeyer–Peppas model. All formulations exhibited strong in vitro antibacterial activity. However, the thermoresponsive gel functionalized with hyaluronic acid (Formula A+) produced the greatest therapeutic effect in diabetic mice, significantly improving wound closure, accompanied by augmented tissue regeneration, complete re-epithelialization, and dermal remodeling, with reduced inflammatory cell infiltration and scarring. These results indicate that this system can provide sustained local antibiotic delivery and promote the healing of infected diabetic ulcers.

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DOI: 10.3897/pharmacia.73.e205931

Authors: Petya Milushewa, Maria Dimitrova, Iva Nenkova, Konstantin Tachkov, Zornitsa Mitkova, Guenka Petrova

Abstract: Population aging and the increasing prevalence of diabetes are contributing to the growing burden of age-related macular degeneration (AMD) and diabetic macular edema (DME) in Bulgaria. This short communication summarizes recent evidence on clinical care pathways and the socioeconomic impact of these conditions, based on published cost-of-illness (COI) and socioeconomic burden analyses. Available data point to substantial losses along the care pathway, with low diagnosis and treatment rates leading to delayed intervention and poorer outcomes. The average annual cost per patient with neovascular AMD in Bulgaria is estimated at €21,722, with most costs arising from reduced quality of life, productivity losses, and welfare losses rather than direct medical care. At the population level, the annual economic burden of neovascular AMD is estimated at €228.9 million. When AMD and DME are considered together, the total socioeconomic burden reached €545.7 million during 2017–2023 and is projected to rise to €1.39 billion by 2032. These findings indicate a considerable and increasing societal impact, highlighting the importance of earlier detection and more coordinated eye care in Bulgaria.

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DOI: 10.3897/pharmacia.73.e206962

Authors: Vesselin Marinov Marinov, Konstantin Ivanov Kostov, Yozlem Ali Kobakova, Angelina Georgieva Kirkova-Bogdanova, Maria Stamova Vakrilova Becheva, Niya Emilova Semerdzhieva, Stefka Achkova Ivanova, Maria Sevdelinova Chaneva, Ventseslava Petrova Atanasova, Yonko Tsvetanov Yonchev, Radoslav Fedeev Todorov, Nikolay Zarkov Bashev, Ismail Elhanov Bashov, Diana Nikolaeva Teneva, Kamen Valentinov Danov, Maria Georgieva Moneva-Sakelarieva, Kiril Todorov Atliev, Vasil Sotirov Kyosev, Silviya Milchova Pavlova, Adel Habib Ibrahim, Petar Yordanov Atanasov

Abstract: Gastric leak after laparoscopic sleeve gastrectomy (SG) is a rare but life-threatening complication requiring timely diagnosis and coordinated multidisciplinary management. Therapeutic options include conservative treatment, percutaneous drainage, endoscopic interventions, and surgical revision. This case describes an early gastric leak successfully managed through a step-up approach combining conservative stabilization, over-the-scope clip (OTSC) closure, and laparoscopic drainage. The case highlights the importance of individualized treatment strategies and the role of minimally invasive endoscopic techniques in selected patients.

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DOI: 10.3897/pharmacia.73.e204360

Authors: Tien-Duc Vo-Ho, Hue Bach Thi Vo, Hoa Van Huynh, Phi-Yen Thi Le, Ngoc-Nhi Thi Nguyen, Trung Quang Vo

Abstract: Background: Self-medication is a common health behavior worldwide, particularly among health sciences students who may overestimate their pharmacological competence. In Vietnam, existing evidence focuses almost exclusively on university students, whereas associate-degree pharmacy and nursing students—the future primary healthcare workforce—have not been systematically compared. Objectives: This study assessed knowledge, attitudes, and practices regarding self-medication and identified independent predictors of this behavior. Methods: A cross-sectional study was conducted from November to December 2025 among 363 final-year students (223 pharmacy students and 140 nursing students) using total sampling at Binh Duong Medical College. A self-administered questionnaire was culturally adapted through a six-stage process; internal consistency reached a Kuder–Richardson 20 coefficient of 0.85 for knowledge and Cronbach’s alpha of 0.92 for attitudes. Data were analyzed using the chi-squared test, the Mann–Whitney U test, and multivariable logistic regression with multicollinearity control. Results: Most students had good knowledge (80.1%), with a higher proportion among pharmacy students than among nursing students (84.3% vs. 73.2%; p = 0.037). Most students showed a moderate propensity toward self-medication (79.7%). The six-month prevalence of self-medication was 53.3% and was markedly higher among pharmacy students (61.0% vs. 40.0%; p < 0.001). Multivariable analysis identified three independent predictors: nursing discipline (odds ratio = 0.43; 95% confidence interval: 0.24–0.75; p = 0.003), attitude score (odds ratio = 1.05; 95% confidence interval: 1.01–1.09; p = 0.009), and a grade point average of 2.00–2.49 (odds ratio = 3.76; 95% confidence interval: 1.13–17.21; p = 0.049). Knowledge score was not significant (p = 0.320). Conclusion: Despite a solid pharmacological foundation, more than half of the final-year students practiced self-medication. Attitudes and training discipline—but not knowledge—were significant independent predictors. Health professional curricula should incorporate attitude-oriented interventions emphasizing the limits of professional competence and clinical risk to promote responsible self-medication.

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DOI: 10.3897/pharmacia.73.e196211

Authors: Amankeldi Sadanov, Gul Baimakhanova, Saltanat Orasymbet, Irina Ratnikova, Baiken Baimakhanova, Irina Smirnova, Aigerim Kantureyeva, Kairat Zhakipbekov, Karakoz Tolenova, Aknur Turgumbayeva

Abstract: Althaea officinalis, a perennial herbaceous plant from the genus Althaea of the Malvaceae family, is recognized for its medicinal properties, particularly in relieving sore throats, dry coughs, stomach ulcers, and wound healing. Modern pharmacological studies have identified its extracts as having several beneficial effects, including antitussive, anti-inflammatory, antioxidant, antibacterial, and wound-healing properties. Chemical analyses have revealed a rich composition of bioactive compounds in the plant, including mucopolysaccharides, flavonoids, phenolic acids, tannins, coumarins, steroids, caffeic acid, ferulic acid, and triterpenoids. The roots and leaves contribute to various edible and medicinal applications, ranging from teas and salads to emollients and sedatives. Althaea officinalis is also cultivated extensively for its ornamental flowers and is found worldwide, playing a significant role in food, healthcare, and dietary supplements. Overall, the plant’s diverse chemical makeup contributes to its pharmacological capabilities, making it a well-known traditional herbal remedy with contemporary relevance. This review aims to provide a comprehensive overview of the chemical constituents and biological characteristics of Althaea officinalis.

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DOI: 10.3897/pharmacia.73.e198333

Authors: Anela Hadžifejzović Trnka, Nermina Žiga Smajić, Selma Škrbo

Abstract: Introduction: Older adults with type 2 diabetes mellitus (T2DM) frequently present with multiple comorbidities and complex therapeutic regimens, increasing the risk of potentially inappropriate medication (PIM) prescribing. This study aimed to assess the prevalence of PIM prescribing in geriatric patients with T2DM using the 2019 American Geriatrics Society Beers Criteria. Materials and methods: This observational, retrospective study included 400 geriatric patients (≥65 years) with T2DM. Data on prescribed medications were collected from medical records. Statistical analysis was performed using SPSS 13.0 and Microsoft Excel 2019 (α = 0.05). Results: At least one PIM was identified in 60.8% of patients. Frequently prescribed PIMs included proton pump inhibitors (13.5%), diazepam (10.3%), and digoxin (6.5%) among medications to be avoided, and diuretics (59.5%) and acetylsalicylic acid (19.0%) among medications to be used with caution. Conclusion: Systematic application of the Beers Criteria may improve pharmacotherapy safety in this vulnerable population.

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DOI: 10.3897/pharmacia.73.e200581

Authors: Hussein K. Alkufi, Omar Saeb Salih, Salam Shanta Taher

Abstract: Background: Ebastine (EBS) is an antihistamine medication commonly used to alleviate symptoms associated with allergic rhinitis and pruritic skin conditions, such as urticaria and other pruritic dermatoses. The main advantage of oral lyophilisates is their high porosity, which facilitates rapid salivary penetration, short disintegration times, and improved bioavailability. Method: EBS-loaded Solusome nanovesicles were formulated via the thin-film hydration technique using Soluplus® as a stabilizing agent within the nanovesicle system. The Solusome nanovesicles were concentrated using a rotary evaporator before the other excipients were added. The excipients used were gelatin, polyvinylpyrrolidone K90, glycine, and mannitol. They were dissolved in the concentrated Solusome nanovesicles, poured into tablet blister molds, and lyophilized to create EBS-loaded Solusome nanovesicle-based oral lyophilisates. Results: The selected formula, F7, had the highest desirability value of 1, and its disintegration time and friability were 31.9 s and 0.991%, respectively. The dissolution profile showed a significant enhancement; more than 98% of the drug was released within only 40 min, whereas pure EBS achieved only 42% release during the same period. Compatibility studies showed that there was no chemical interaction between the tablet components. An in vivo bioavailability study of EBS showed that Solusome nanovesicles enhanced bioavailability compared with pure EBS. Discussion: A notable improvement was observed in both the disintegration time and friability tests. The highly porous structure of oral lyophilisates allows rapid salivary penetration, resulting in very short disintegration times and enhanced bioavailability. Soluplus® can spontaneously form spherical micelles. Furthermore, the polyethylene glycol (PEG) segment of Soluplus® promotes the formation of stable, tightly packed bilayers, thereby reducing particle aggregation and preventing the formation of large vesicular structures. Conclusion: This study aimed to develop EBS Solusome nanovesicles as oral lyophilisates. The primary goal was to improve tablet disintegration in the mouth, facilitate easier swallowing, and potentially enhance patient compliance. Additionally, the researchers aimed to achieve faster disintegration times for oral lyophilisates, thereby accelerating the onset of EBS therapeutic action.

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DOI: 10.3897/pharmacia.73.e184854

Authors: Liliya Stoyanova, Miroslava Benkova-Petrova, Aleksandar Petrov, Pavel Abushev, Simeon Marinov, Martina Stoeva, Yavor Petrov

Abstract: Introduction: Transfusion-dependent β-thalassemia major (β-TM) is increasingly complicated by renal injury related to iron overload and chelation. This study aimed to evaluate albuminuria/proteinuria in β-TM and their association with chelation regimen. Methods: Cross-sectional single-center study (2018–2019) of 44 β-TM patients and 30 controls. Patients received deferasirox (Exjade), deferiprone (Ferriprox), deferoxamine (Desferal), or combined deferiprone+deferoxamine. Serum creatinine and estimated creatinine clearance (Schwartz/MDRD) were recorded; first-morning urine albumin/protein and creatinine were used to compute ACR and PCR. Results: ACR and PCR were higher in β-TM than controls (p=0.015; p=0.023) and increased with age, peaking at 48–57 years (ACR 20.9 g/mol; PCR 42.0 g/mol). Deferasirox showed the highest ACR/PCR, followed by deferiprone and deferoxamine; combined therapy had the lowest values. Conclusions: Albuminuria and proteinuria are common in β-TM and relate to age and chelation type, supporting routine ACR/PCR monitoring and individualized chelation to reduce nephrotoxicity.

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DOI: 10.3897/pharmacia.73.e203259

Authors: Maya Vizeva, Stoyan Vizev, Rossen Mihaylov, Evelin Hayvazov

Abstract: Chronic diseases, multimorbidity, and the prolonged use of medications are gradually transforming pharmacotherapy into a long-term and organizationally complex process involving numerous participants and sources of information. This article aims to analyze the organizational implications of prolonged multiprofessional pharmacotherapy in chronic diseases and the importance of the traceability, consistency, and connectivity of information to the quality and sustainability of treatment. A conceptual and analytical approach was applied based on a thematic and interpretive review of the scientific literature related to chronic diseases, long-term pharmacotherapy, interprofessional collaboration, continuity of care, and the role of the patient. The findings indicate that as the duration of treatment increases, decisions, participants, and sources of information gradually accumulate, increasing the organizational complexity of treatment and its dependence on information traceability and connectivity. This creates conditions for partial therapeutic visibility, organizational vulnerability, and disrupted continuity in long-term multiprofessional pharmacotherapy. The role of the patient becomes particularly important, as they often remain the most consistent participant in treatment while simultaneously bearing the consequences of insufficient coordination and incomplete information. Improved traceability, professional coordination, documentation, pharmaceutical care, and digital support may contribute to greater safety, sustainability, and quality of long-term pharmacotherapy in chronic diseases.

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DOI: 10.3897/pharmacia.73.e205309

Authors: Ahmed Nedzhib, Silviya Stoykova, Alexander Zlatkov, Ivan Samnaliev

Abstract: Available evidence indicates that A-series (“Novichok”) nerve agents are highly toxic organophosphorus compounds whose primary mechanism of action involves potent inhibition of acetylcholinesterase, resulting in severe cholinergic toxicity and potentially prolonged neurological consequences. Recent analytical advances, including high-resolution mass spectrometry and protein adduct analysis, have substantially improved exposure verification and forensic attribution. Current data support the use of established nerve agent treatment principles, including atropine, oximes, benzodiazepines, and intensive supportive care, although evidence regarding oxime responsiveness and aging kinetics remains limited for several compounds. Existing knowledge of environmental persistence, toxicokinetics, and long-term health effects is constrained by the scarcity of authenticated reference materials and experimental studies. Computational toxicology and machine-learning approaches have provided valuable mechanistic insights but require further experimental validation. Continued multidisciplinary integration of toxicology, analytical chemistry, computational modeling, medicinal chemistry, and public health preparedness will therefore remain essential for improving scientific understanding and response capabilities related to emerging organophosphorus threats.

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DOI: 10.3897/pharmacia.73.e197283

Authors: Diana D. Stoyanova, Anna H. Todorova, Magdalena T. Pesheva, Evgeni E. Grigorov

Abstract: Regulation of medicinal products containing controlled substances varies considerably across Europe, despite a shared international and EU legal framework. A comparative normative analysis of national legislation in 10 European jurisdictions (nine EU Member States and the United Kingdom), structured around seven predefined criteria, ascertained four regulatory models: (1) Centralized–Procedural (France, Germany, Italy, and Greece); (2) Digitalized–Integrated (Belgium and Poland); (3) Harm-Reduction (Netherlands and Portugal); and (4) Institutional Accountability (United Kingdom and Ireland; Ireland shares features of Models 1 and 4). Substantial variation was observed in digitalization levels, document retention requirements (2–10 years), and destruction procedures. The findings highlight persistent regulatory fragmentation and underscore the need for minimum common standards for traceability and digitization while preserving national flexibility. The role of hospital pharmacists as a critical legal–clinical interface warrants explicit recognition in future harmonization efforts.

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DOI: 10.3897/pharmacia.73.e194529

Authors: Emilio Mateev, Diana Tzankova, Valentin Karatchobanov, Ali Irfan, Eva-Maria Pepeldzhiyska, Stefan Kostov, Alexander Zlatkov

Abstract: Twenty novel pyrrole-based hydrazide-hydrazone derivatives (GlyOH1-4, BAlaOH1-4, IleOH1-4, PheOH1-4, TrpOH1-4), bearing hydroxyl-substituted aromatic aldehydes and diverse amino acid scaffolds, were designed, synthesized in 83-95% yields, and fully characterized by FT-IR, 1H-NMR and 13C-NMR. All compounds exhibited radical-scavenging activity in DPPH and ABTS assays, with TrpOH-3 emerging as the lead (IC50 3.96 ± 0.20 μM ABTS, 9.17 ± 0.09 μM DPPH), outperforming Trolox in both. SAR analysis revealed optimal activity from tryptophan scaffolds and catechol-like (2,3,4- or 2,4,5-trihydroxy) moieties, attributed to enhanced HAT/SET mechanisms and radical stabilization. Molecular docking of TrpOH-3 to Keap1 Kelch domain (PDB: 4L7B) yielded -6.25 kcal/mol, featuring H-bonds (Ser602, Ser363, Tyr525), water-mediated interactions, and Br-Tyr334 halogen bonding, supporting Nrf2 activation potential. ADME predictions indicated drug-likeness (1 Ro5 violation), though high MW limited CNS permeability. These multifunctional antioxidants hold promise for oxidative stress-related disorders.

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DOI: 10.3897/pharmacia.73.e200091

Authors: Fildza Huwaina Fathnin, Satibi Satibi, Dwi Endarti, Lutfan Lazuardi

Abstract: Inadequate household medication management may lead to health risks and economic losses related to leftover, damaged, or expired medicines. This study aimed to evaluate the impact of the “Kelola Obatku” mobile application on knowledge, attitudes, and practices (KAP) and medicine-related economic values. A quasi-experimental pretest–posttest study with control and intervention groups was conducted among 60 adult respondents in Central Java, Indonesia, between August and November 2025. The intervention group used the mobile application for 3 months. Data were collected using validated questionnaires, and economic values were calculated in Indonesian rupiah based on the maximum retail price stated on medicine packaging. The application demonstrated acceptable usability, with an overall score of 80.33%. Between-group analysis showed significant improvements in knowledge and attitudes based on delta scores (p = 0.001 and p = 0.017, respectively), while practice did not improve significantly. No significant between-group differences were observed in medicine-related economic values. However, within-group analysis in the intervention group showed significant reductions in damaged and expired medicine values (p = 0.023 and p = 0.047, respectively). These findings suggest that the application may improve knowledge and attitudes and support better identification of damaged and expired medicines.

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DOI: 10.3897/pharmacia.73.e204540

Authors: Sofiya Mihaylova, Guenka Petrova

Abstract: Objective: To explore the economic and social impact of obesity in Bulgaria and to examine its burden on public health and society. Methods: This study is a quantitative cost-of-illness (COI) analysis from a societal perspective, focusing on the adult population with obesity (BMI ≥ 30 kg/m2). Direct medical costs (medication costs, hospitalisations, bariatric surgery, and complications such as diabetes, cardiovascular complications, and surgical complications) and indirect costs were calculated during the first half of 2025. The social burden was estimated through disability-adjusted life years (DALYs). Results: Epidemiological data show that two-thirds of the population is expected to have a high BMI or obesity, and these numbers will increase substantially until 2030. Direct healthcare costs accounted for €55 935 208.00 for a 6-month period, with hospitalisations due to complications (47%) and anti-obesity medicines (48%) having the leading shares. The minimal value of indirect costs generated due to absenteeism was €57 922 356.06 for the first 6 months of 2025. DALYs calculated for major obesity complications accounted for €42 468 for 1 year. Years of life lost due to premature death were the larger contributor to DALYs. Conclusions: Obesity is a widespread chronic disease with a high prevalence in Bulgaria, consistent with global trends. It is associated with substantial healthcare costs, productivity losses, and DALYs. The indirect costs related to obesity are slightly higher in the country than the direct costs of its treatment. Total DALYs related to obesity are also significant. Diabetes and cardiovascular diseases are the main contributors to DALYs due to obesity in Bulgaria.

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DOI: 10.3897/pharmacia.73.e196917

Authors: Oleksandr Komarida, Kostyantyn Kosyachenko, Nataliia Sakhnatska

Abstract: The study aimed to assess the awareness, attitudes, and readiness of pharmaceutical professionals in Ukraine regarding the implementation of pharmacist prescribing. In 2025, a nationwide cross-sectional online survey was conducted among 1,020 pharmacists. The results showed low awareness of international prescribing models, with only 9.0% reporting sufficient knowledge. Attitudes were mixed: 13.9% supported implementation, while 61.6% expressed negative or somewhat negative views. Support correlated with the level of professional autonomy, with collaborative models preferred over independent ones. Key perceived benefits included improved access to pharmacotherapy and reduced physician workload. Major barriers identified were the lack of a clear regulatory framework, limited access to patient medical records, insufficient interprofessional collaboration, and concerns about professional liability. Additionally, 92.9% reported insufficient knowledge, and only approximately one-third were willing to undergo specialized training. Practice-based workplace training was considered most effective. Overall, the findings support phased implementation focused on collaborative models, regulatory development, and structured postgraduate education.

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DOI: 10.3897/pharmacia.73.e203129

Authors: Tanya Gesheva, Nedyalka Boycheva, Gergana Todorova, Anna Mihaylova

Abstract: Background: Cannabidiol (CBD) has gained increasing scientific and clinical attention because of its potential therapeutic effects in chronic pain, anxiety, and neurodegenerative disorders. Patients with neurodegenerative diseases frequently experience persistent pain, emotional distress, and reduced quality of life, leading to growing interest in complementary therapeutic approaches, such as CBD products. Aim: The aim of the present study was to evaluate the awareness, attitudes, and willingness to use CBD products among Bulgarian patients with neurodegenerative diseases and chronic pain. Materials and methods: A cross-sectional survey study was conducted among 55 adult patients experiencing chronic pain, including individuals diagnosed with Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, and multiple sclerosis. Data were collected using a structured questionnaire assessing demographic characteristics, awareness of CBD products, pain intensity, anxiety levels, and willingness to use CBD products. Statistical analyses included descriptive statistics, the Mann–Whitney U test, Fisher’s exact test, Pearson’s chi-square test, and Spearman correlation analysis. Results: Most participants (61.8%) reported prior awareness of CBD products, while 85.5% expressed willingness to use CBD if recommended by a healthcare professional. Significant associations were identified between CBD awareness and willingness to use CBD products, as well as between awareness and previous CBD use. Participants informed about CBD reported higher levels of chronic pain and anxiety compared with uninformed respondents. A moderate positive correlation was observed between pain intensity and anxiety levels. Patients with neurodegenerative diseases demonstrated higher anxiety levels compared with respondents without neurodegenerative conditions. Conclusion: Bulgarian patients with chronic pain and neurodegenerative diseases demonstrate substantial interest in CBD products as complementary therapeutic agents. However, insufficient patient awareness and limited medical guidance remain important barriers to the safe therapeutic integration of CBD products.

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DOI: 10.3897/pharmacia.73.e167649

Authors: Petar Stoilov, Antoaneta Mihova, Rosen Mihaylov, Stanislava Zlateva, Poli Dimcheva, Eugeni Pentchev, Marinela Kalcheva, Blagovesta Pencheva, Emilia Naseva, Tsvetelina Velikova

Abstract: The assessment of antigen-specific IFNγ immune response to Mycobacterium tuberculosis antigens is primarily conducted using two tests: QuantiFERON-TB (QFT) and T-SPOT.TB. The cell-mediated reaction on which both tests are based is crucial for distinguishing between latent and active tuberculosis (TB), particularly in patients receiving biological therapy. Our objective is to compare the results of patients tested with both methods, either simultaneously or within defined time intervals (up to one year). Whole venous blood (peripheral mononuclear cells, PBMCs) from patients were processed using QuantiFERON-TB Gold Plus (QFT-Plus), Qiagen, and T-SPOT.TB, Oxford Immunotec. Between January 1 and December 31, 2024, a total of 7,392 patient samples were tested in the Ramus laboratory — 6,887 with QFT-Plus and 505 with T-SPOT.TB. The analysis expectedly showed a prevalence of negative results, at 92.3% and 59.8%, compared to positive results, at 5.3% and 24.6%, respectively, for QFT-Plus and T-SPOT.TB. Low values of borderline and indeterminate results were around 2% for QFT-Plus, but 5.7% and 9.5% for T-SPOT.TB. The indeterminate results for T-SPOT.TB were reduced to 5.3% because some of them (21 patients) were on biological therapy and subsequently became negative. We analyzed the results of 94 patients who underwent both tests and 12 patients who were tested multiple times with one method during the year. Concordance between the two tests was observed in 51 individuals (54.3%): 31 had concordant positive results, 17 had concordant negative results, and 3 had indeterminate results in both tests. Discrepancies were found in 43 patients (45.7%). The analysis showed that in 61% of these cases (26/43), results shifted from indeterminate/borderline to negative or vice versa within 1 to 6 months—an acceptable variability. Among the remaining 17 individuals (39%) whose results changed from positive to negative or indeterminate, further analysis revealed that all had initiated biological therapy. Among the 12 patients repeatedly tested with T-SPOT.TB over 4–8 months, three showed consistent positive results, two showed consistent negative results, and seven experienced changes, all of whom were on biological therapy. The results from both IFNγ-based tests are comparable, with acceptable variation over time. Clinicians can rely on either method; however, significant result changes should be interpreted in light of ongoing specific or biological therapy.

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DOI: 10.3897/pharmacia.73.e194858

Authors: Ameer Almubarak, Manal Khalid Abdulridha

Abstract: In this cross-sectional questionnaire-based study conducted in Karbala, Iraq, between September and October 2025, 360 physicians, pharmacists, and dentists completed a survey. The mean total knowledge, attitude, and practice (KAP) score was 3.594/5, with attitude scoring highest, followed by practice and knowledge. Physicians had significantly higher total KAP scores than pharmacists and dentists; in adjusted analysis, physicians scored higher than dentists (B = 0.148, p = 0.008). Overall, 26.4% had heard of the WHO Access, Watch, and Reserve (AWaRe) classification; awareness was highest among pharmacists (50.8%) compared with physicians (15.0%) and dentists (13.3%). Pharmacists had higher odds of AWaRe awareness than physicians (adjusted OR = 5.284, 95% CI 2.443–11.432; p < 0.001). Total KAP correlated positively with AWaRe perception among aware participants (Spearman’s ρ = 0.344, p = 0.001). These findings support the parallel strengthening of stewardship education and AWaRe implementation..

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DOI: 10.3897/pharmacia.73.e198293

Authors: Maria Nikolova, Adolf Alakidi, Radka Tafradjiiska-Hadjiolova, Valentina Petkova, Adriana Agovska

Abstract: Objectives: Vitamin D deficiency has been associated with obesity, insulin resistance, chronic inflammation, and cardiovascular disease (CVD). This study aimed to evaluate the association between serum vitamin D concentrations, body mass index (BMI), and cardiometabolic risk factors in adults. Methods: A cross-sectional observational study was conducted among 264 adults (109 men and 155 women) aged 19–60 years (mean age, 41.19 years). Anthropometric measurements, body composition parameters, blood pressure, biochemical markers, and questionnaire-derived health information were assessed. Participants were classified according to serum 25-hydroxyvitamin D [25(OH)D] concentrations and BMI status. Statistical analyses included the χ2 test, Fisher’s exact test, Student’s t-test, ANOVA, Spearman correlation analysis, and multiple linear regression. Results: CVD was more prevalent among participants with vitamin D deficiency than among those with sufficient vitamin D concentrations (15.9% vs. 7.1%, p < 0.01). Obesity (70.5% vs. 48.6%, p < 0.001), diabetes (8.0% vs. 4.3%, p < 0.001), and depression (25.0% vs. 10.0%, p < 0.001) were also more common in the vitamin D-deficient group. Serum 25(OH)D concentrations were inversely associated with BMI, waist circumference, waist-to-height ratio, fat mass, triglycerides, fasting insulin, HOMA-IR, and hsCRP. Serum 25(OH)D concentrations decreased significantly across BMI categories, from 48.8 nmol/L in normal-weight participants to 22.2 nmol/L in those with class III obesity (p < 0.001). Individuals with vitamin D deficiency had a longer history of overweight or obesity (14.95 ± 9.40 vs. 10.85 ± 6.24 years, p < 0.01). BMI, waist-to-height ratio, body fat percentage, and lipid ratios demonstrated the strongest predictive value for serum 25(OH)D concentrations. Conclusion: Vitamin D deficiency is associated with an unfavorable cardiometabolic profile characterized by increased adiposity, insulin resistance, inflammation, and a higher prevalence of CVD. The coexistence of vitamin D deficiency and excess BMI may further increase cardiometabolic risk and should be considered in preventive and clinical risk assessment strategies.

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DOI: 10.3897/pharmacia.73.e192841

Authors: Veselina Goranova-Marinova, Zlatka Dimitrova, Kalina Andreevska, Daniela Grekova, Vania Georgieva, Vassil Madzharov, Dimana Dimitrova, Valentina Petkova

Abstract: Introduction: Chronic myelogenous leukemia (CML) is a malignant disease of the pluripotent hematopoietic stem cell, characterized by the presence of the BCR-ABL1 fusion gene, resulting from a balanced translocation between the long arms of chromosomes 9 and 22 [t(9;22)(q34;q11)], known as the Philadelphia (Ph) chromosome. CML is an acquired disease of the hematopoietic stem cell, common to myelo- and lymphopoiesis, characterized by the uncontrolled proliferation of granulopoiesis—current status and goals. The introduction of targeted therapy with tyrosine kinase inhibitors (TKIs) for this rare, life-threatening disease has turned it into a chronic disease that can be controlled in over 90% of cases. Second-generation TKIs (nilotinib, dasatinib, and bosutinib) have an advantage over imatinib (first-generation) in terms of the frequency and speed of achieving cytogenetic and molecular responses in CML. However, they cause more severe adverse effects and are much more expensive than imatinib, especially when compared with the prices of several already registered generic products of imatinib and dasatinib. On the other hand, the constantly increasing costs of diagnosis, treatment, and monitoring of the response of CML to different therapeutic strategies require periodic pharmacoeconomic analyses of the cost-effectiveness, cost-benefit, and cost-utility types to assess which therapeutic strategies are cost-effective for a given period and in the long term, including due to changes in the annual costs of treatment when cheaper generic products for some strategies appear on the pharmaceutical market, with a view to their use in therapeutic practice. In addition, over the past decade, patients with CML who have achieved a stable deep molecular response for at least 2–3 years have been enrolled in large-scale clinical trials evaluating treatment-free remission (TFR). The present study aims to analyze and estimate savings from a portion of the costs of drug therapy under different strategies that include patients in remission in the so-called treatment-free phase of first- and second-line therapy for chronic-phase CML (CML-CP). The research perspective is that of the payer—the National Health Insurance Fund (NHIF)—and the cost research horizon is 20 one-year cycles. Methods: A diagram of a general Markov model of CML disease, including the three disease phases and possible transitions among health states, including death, was developed. Two alternative pharmacoeconomic Markov chain models were also developed. One is a model of the diagnosis and continuous treatment of CML-CP in the first and second lines of CML-CP treatment until the end of the patients’ lives, i.e., a standard model without the TFR phase, and the second is an extended model with the TFR1 and TFR2 phases included, i.e., with the inclusion of the TFR phase in both lines of CML-CP. The transition probabilities between states were extracted from real clinical data, with missing annual values imputed using the median. The analysis was conducted over 20 years. Both costs and health effects were discounted by 3% per year, in accordance with established pharmacoeconomic practices. Costs are based on annualized drug therapy costs for each treatment line. Health effects are measured in quality-adjusted life years (QALYs), assuming a utility value of 0.92 for all living health states, as reported in the literature. Transition to the TFR phase is defined as achieving a deep molecular response (MR4.5 log or MR5 log) after first- or second-line therapy. The duration of stay in the TFR phase is 5–7 years, assuming 50% of patients return to their respective treatment lines.

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DOI: 10.3897/pharmacia.73.e200497

Authors: Ali Olamat, Hamza Abu Owida, Areen Arabiat, Pinar Ozel

Abstract: A data-driven approach was developed to model microfluidic liposome formulation and predict two important quality attributes: particle size (SIZE) and polydispersity index (PDI). The data set contained 306 formulations with process factors (e.g., flow rate ratio and total flow rate) and formulation factors, supported by initial exploratory analysis (feature engineering) and interpretability analysis. Eleven machine learning (ML) and deep learning (DL) models were tested. Predictions of PDI were highly accurate, with the best validation performance achieved with gradient boosting (R2 = 0.765; RMSE = 0.106; MAE = 0.059), which exceeded a previously reported benchmark. However, predictions of SIZE were much less accurate than those of PDI, with the best validation performance achieved with a deep multilayer perceptron (R2 = 0.460), which is consistent with the presence of target skewness and outliers in the size data. Both feature importance and SHAP analyses indicated that engineered ratios of the formulation composition, particularly the main lipid-to-PEG ratio, along with process effects, such as the flow rate ratio (FRR), were primary contributors to the prediction of PDI. Overall, the findings provide evidence supporting the application of explainable ML to direct the development of microfluidic liposomes, specifically for improving formulation uniformity, while indicating the need for larger and more robust data sets and strategies to improve the accuracy of size predictions.

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DOI: 10.3897/pharmacia.73.e190953

Authors: Lely Retno Wulandari, Intan Kautsarani, Rofiqi Rofiq, Edwin Damar Prabowo, Hidayat Sujuti, Happy Kurnia Permatasari, Sri Winarsih

Abstract: Posterior capsular opacification (PCO) arises from fibrotic activation of residual lens epithelial cells (LECs) after cataract surgery. Connective tissue growth factor (CTGF) serves as a pivotal downstream amplifier of transforming growth factor-β2 (TGF-β2)-induced signaling, promoting the fibrotic cascade. This study evaluated the effect of pamrevlumab, a CTGF-neutralizing antibody, on profibrotic signaling in a primary pediatric LEC culture model. β-catenin, ERK phosphorylation, and collagen type I (COL-1) expression were analyzed by immunofluorescence, whereas proliferation and migration were assessed using a wound-healing assay. Pamrevlumab significantly suppressed β-catenin nuclear activation (p = 0.023) and COL-1 expression (p < 0.001) in a dose-dependent manner, whereas ERK signaling showed no significant difference (p > 0.05). Regression analysis estimated a potent reduction of 608.40 AU in COL-1 expression for every 1 μg/mL increase in pamrevlumab dose (p = 0.001). These results indicate that pamrevlumab ameliorates CTGF/β-catenin-associated profibrotic signaling and prevents coordinated fibrotic responses in primary human LECs. Although this study is limited to an in vitro mechanistic context, it ultimately lays the preclinical groundwork for further translational exploration of CTGF-targeted approaches for the mitigation of PCO.

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DOI: 10.3897/pharmacia.73.e188976

Authors: Yoana Kiselova-Kaneva, Zhechko Dimitrov, Ignat Ignatov, Teodora Popova, Irina Gotova, Teodora Todorova, Krassimir Boyadzhiev, Ivan Angushev, Diana Ivanova

Abstract: This study examined the polyphenol composition, antioxidant properties, and biological activity of bilberry (Vaccinium myrtillus L.) fruit juice from Bulgaria. Antioxidant potential was analyzed using ABTS (2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)), DPPH (2,2-diphenyl-1-picrylhydrazyl), and FRAP (ferric reducing antioxidant power) methods. Total polyphenol, flavonoid, and anthocyanin contents were measured using colorimetric methods. Specific anthocyanin content was measured by UPLC-MS/MS. Cytoprotective and superoxide anion radical-scavenging activities were analyzed in in vitro Saccharomyces cerevisiae experiments. UPLC-MS/MS analysis revealed a total anthocyanin content of 338.5 mg/100 g fresh fruits, and the dominant compounds were malvidins (38.1%), delphinidins (33.2%), petunidins (18.6%), and cyanidins (10.1%). Total polyphenol content was 8.40 ± 0.29 mg GAE/100 mL, and total flavonoid content was 7.26 ± 0.11 mg QE/100 mL. Antioxidant potential was as follows: ABTS (3.6 ± 0.08 mM UAE), DPPH (89 ± 2.1%), and FRAP (2.4 ± 0.09 mM Fe(II)/L). Cell-based assays demonstrated significant cytoprotective activity and reduced methyl methanesulfonate-induced superoxide anions. These results demonstrate the value of Bulgarian bilberry juice as a source of bioactive compounds and as a potential raw material for the pharmaceutical and nutritional industries.

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DOI: 10.3897/pharmacia.73.e191017

Authors: Regina Nababan, Yahdiana Harahap, Febrina Amelia Saputri

Abstract: Rivastigmine is a cholinesterase inhibitor widely used for the symptomatic treatment of Alzheimer’s disease and Parkinson’s disease dementia. Its therapeutic action occurs primarily in the central nervous system, making brain distribution a critical determinant of clinical efficacy. After administration, rivastigmine is rapidly absorbed, exhibits a short elimination half-life, and readily crosses the blood–brain barrier. Consequently, plasma concentrations are very low and decline rapidly, and circulating levels may not directly reflect drug exposure at the target site. These pharmacokinetic characteristics support the evaluation of bioanalytical methods and their potential relevance to therapeutic drug monitoring in specific contexts. This review evaluates published bioanalytical methods for rivastigmine determination and their relevance to pharmacokinetic studies and therapeutic drug monitoring. Eleven validated studies (2003–2026) were analyzed, including analyses in human plasma, animal plasma, brain tissue, and urine. Plasma is primarily used to assess systemic exposure, while brain tissue confirms central distribution, and urine supports excretion profiling. However, endogenous proteins and phospholipids frequently cause matrix effects, necessitating sample preparation techniques such as protein precipitation, liquid–liquid extraction, and solid-phase extraction. Across studies, liquid chromatography–tandem mass spectrometry (LC–MS/MS) has become the dominant analytical approach due to its superior sensitivity, enabling picogram-level quantification that supports reliable pharmacokinetic profiling at low concentrations. Therapeutic drug monitoring has been discussed in relation to interindividual variability and concentration-related cholinergic adverse effects. However, its clinical applicability remains context-dependent and not yet fully established. Overall, rivastigmine biodistribution defines bioanalytical requirements, and the selection of analytical methods should be aligned with specific study objectives. Highly sensitive chromatographic techniques are advantageous for characterizing low systemic concentrations, while other validated methods may remain appropriate depending on the required detection limits and research context.

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DOI: 10.3897/pharmacia.73.e202303

Authors: Dimitar Mirchev, Elina Petkova-Gueorguieva

Abstract: Greek anatomical terminology represents a historically continuous linguistic foundation of modern medical and pharmaceutical sciences. This study examines the development, etymological structure, and educational significance of Greek-derived anatomical terms within standardized anatomical nomenclature. The analysis indicates that many Greek terms preserve semantic transparency, metaphorical imagery, and conceptual precision, whereas their Latinized forms often create challenges related to declension, pronunciation, and interdisciplinary comprehension. Terms such as trachea, aorta, arteria, thalamus, encephalon, pharynx, and skeleton demonstrate how anatomical naming combines descriptive, functional, and metaphorical principles. The findings indicate that etymology-based instruction, problem-based learning, visual resources, and curricular integration can improve terminology acquisition in medical and pharmaceutical education. Understanding the historical and linguistic foundations of anatomical terminology strengthens professional communication, terminological accuracy, and interdisciplinary competence in contemporary healthcare.

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DOI: 10.3897/pharmacia.73.e185272

Authors: Stefeny Theresia Simatupang, Doni Dermawan, Nadia, Santi Tan, Adi Yulandi, Raymond Rubianto Tjandrawinata

Abstract: Pathogenic single-nucleotide variants (SNVs) in the ABCC8 gene have been associated with susceptibility to type 2 diabetes (T2D), and understanding how these variants alter protein structure is crucial for the development of personalized therapeutic strategies for T2D. Gliclazide binding to ABCC8 variants was assessed using molecular docking, 50 ns molecular dynamics simulation (MDS), and MM-PBSA. Docking indicated a conserved pose with affinity shifts; an Arg1144 hydrogen bond persisted in all variants, whereas the wild type (WT) engaged Tyr1293. More favorable docking energies coincided with π–π or π–sulfur contacts involving Trp1296 and Phe591/Tyr1293 or His584. Complexes remained stable during simulation, showing RMSD plateaus, stabilized radius of gyration and solvent-accessible surface area (SASA) after equilibration, and maintained ligand–receptor distances. Phe591Leu showed the most stable profile, whereas Asp1471Asn exhibited deviation. MM-PBSA predicted the strongest binding for the wild type (−21.86 ± 2.70 kcal/mol) and weaker, variant-dependent binding for mutants (−19.46 ± 3.33 to −16.34 ± 2.46 kcal/mol), supporting preserved binding. Experimental validation is required to investigate these variants in KATP function and clinical response.

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DOI: 10.3897/pharmacia.73.e198051

Authors: Boryana Borisova, Veronica Nemska, Hristina Zlatanova-Tenisheva, Marie Laronze-Cochard, Stéphane Gérard, Petya Romanova, Anargyros N. Moulas, Dancho Danalev

Abstract: Inflammation is part of the defense mechanism of the organism, which provokes different signaling pathways. It is also related to several inflammatory mediators, such as cytokines and enzymes from the phosphodiesterase group, especially phosphodiesterase 4 (PDE4). On the other hand, peptides play diverse physiological roles as neurotransmitters, neuromodulators, hormones, and enzyme modulators. Taking these facts into account, the anti-inflammatory activity of several C-terminal amide analogs of tetrapeptide Phe-Glu-Leu-Leu was investigated using the carrageenan-induced paw edema model, and their inhibitory activity against PDE4 was evaluated. It was found that Val and Ile substitutions at positions 3 and 4 improved anti-inflammatory activity in vivo, with compounds BB3 and BB4 producing statistically significant reductions in carrageenan-induced edema at the 3 h time point, although these effects were not sustained at later observations. However, the same substitutions did not consistently enhance PDE4 inhibition. The parent compounds BB1 (C-terminal amide) and BB11 (C-terminal free acid) demonstrated the most balanced overall profile, combining moderate PDE4 inhibitory activity (49% and 58% inhibition at a concentration of 5 mM, respectively) with favorable in vivo anti-inflammatory properties. These findings highlight the complex relationship between peptide structure, PDE4 inhibition, and anti-inflammatory efficacy.

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DOI: 10.3897/pharmacia.73.e200746

Authors: Yulina Gurbeva, Lyubomira Radeva, Lily Peikova, Magdalena Kondeva-Burdina, Krassimira Yoncheva, Maya Georgieva

Abstract: The azomethine compound Y3 was synthesized via a classical condensation reaction between the corresponding hydrazide and aldehyde, using glacial acetic acid as a catalyst, yielding a pure solid product. Y3 and its micellar formulation (Y3_micelles) showed no statistically significant MAO-A/B inhibitory activity at 1 μg/mL. At 100 μg/mL, both compounds induced low neurotoxicity in isolated rat brain synaptosomes, mitochondria, and microsomes, with Y3_micelles exhibiting lower toxicity than Y3. In models of induced neurotoxicity, including 6-hydroxydopamine (6-OHDA), tert-butyl hydroperoxide (t-BuOOH), and iron/ascorbate-induced damage (Fe2+/AA), both compounds demonstrated significant neuroprotective and antioxidant effects at 50 μg/mL. Y3_micelles showed stronger neuroprotective and antioxidant activity compared with Y3. The results indicate that micellar incorporation enhances the safety and neuroprotective potential of Y3.

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DOI: 10.3897/pharmacia.73.e193264

Authors: Idah Rosidah, Ngatinem Ngatinem, Agus Himawan Subiantoro, Susi Kusumaningrum, Firdayani Firdayani, Agung Eru Wibowo, Abdul Mun’im

Abstract: Ardisia elliptica Thunb. (AET) has been recognized as a source of natural active ingredients with antioxidant and anti-aging properties. However, its mode of action remains inadequately elucidated. This study aims to characterize the phytochemical profile and evaluate the antioxidant and collagenase- and elastase-inhibitory activities of AET extract in vitro, as well as elucidate the potential interaction mechanisms of the compounds with enzyme active sites through molecular docking. Different plant parts (leaves, flowers, and fruits) were extracted using 70% ethanol by ultrasound-assisted extraction followed by maceration. Phytochemical analysis encompassed the quantification of total phenolic and flavonoid contents and metabolite profiling using liquid chromatography coupled with Orbitrap high-resolution mass spectrometry (LC-HRMS). Antioxidant activities were measured using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays. The leaf extract demonstrated the highest total phenolic content and antioxidant activity, with IC50 values of 54.21 ± 2.21 and 43.73 ± 0.64 μg/mL for DPPH and ABTS, respectively. Furthermore, it showed significant collagenase- and elastase-inhibitory activities, with IC50 values of 104.11 ± 11.20 and 294.67 ± 8.52 μg/mL, respectively. Its collagenase-inhibitory activity was comparable to that of the positive control, epigallocatechin gallate (EGCG), but remained lower for elastase inhibition. Additionally, molecular docking predicted the strong potential of bilobol, α-linolenic acid, and monoolein as collagenase inhibitors, with MolDock scores of −131, −121, and −119, respectively. Monoolein, bilobol, and erucamide exhibited potential elastase-inhibitory activity, with MolDock scores of −139, −133, and −129, respectively. These findings highlight AET leaf extract as a promising natural candidate for the development of phytocosmetic products, particularly for anti-aging applications with collagenase- and elastase-inhibitory mechanisms.

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DOI: 10.3897/pharmacia.73.e193523

Authors: Rosena Krushovalieva

Abstract: Liposomes are widely investigated drug delivery systems because of their biocompatibility, ability to encapsulate hydrophilic and lipophilic compounds, and capacity to prolong drug release. In ophthalmic delivery, liposomes may improve drug retention on the ocular surface and reduce the rapid precorneal elimination associated with conventional eye drops. Such systems have attracted increasing interest as potential carriers for ocular drug delivery. Stearylamine is a positively charged lipid capable of modifying membrane properties and influencing interactions with negatively charged ocular structures. The aim of the present study was to develop and characterize liposomal formulations containing graded concentrations of stearylamine and to evaluate its effect on the physicochemical properties of liposomes containing timolol maleate. The formulations were characterized in terms of particle size, zeta potential, encapsulation efficiency, release profiles, and stability.

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DOI: 10.3897/pharmacia.73.e194751

Authors: Ahmed Mazin, Monther F. Mahdi, Ayad Kareem Khan

Abstract: Several ketoprofen thiazolidin-4-one hybrids were designed and evaluated to determine whether they could be used as anti-inflammatory drugs. The synthesis involved converting ketoprofen into the methyl ester and hydrazide. Then, the hydrazide was reacted with different benzaldehydes to produce hydrazones, and finally, cyclization with thioglycolic acid produced the thiazolidin-4-one derivatives. FT-IR, 1H NMR, and 13C NMR spectroscopy were used to determine the structures. In silico ADME predictions showed that the compounds had generally acceptable drug-like properties. All derivatives had a molecular weight below 500 Da, and the predicted values for human oral absorption ranged from 87.473% to 100%. Solubility, however, was identified as a possible problem for several analogues. Molecular docking against COX-2 (PDB ID: 5KIR) showed good binding across the series. AR1 had the best GOLD PLP fitness score (81.10), AR5 had the best Glide XP score (–13.685), AR3 had the best IFD score (–2435.132), and AR7 had the best MM-GBSA binding energy (ΔGbind = –73.136). The molecular dynamics simulation of the AR1–COX-2 complex spanning 100.102 ns supported a stable protein–ligand association during the simulated timescale, with ongoing interactions involving Tyr385, Tyr355, Arg120, and Glu524. The anti-inflammatory effects were evaluated in vivo using the egg-white-induced paw edema model in mice. The longitudinal mixed-effects analysis indicated significant influences of treatment, duration, and the interaction between treatment and time. AR3 showed the most consistent late-phase anti-edema activity, including greater efficacy than ketoprofen at the 240 min time point, whereas AR1 remained notable mainly because of its strong computational profile and late-phase activity vs. vehicle control. These results collectively suggest that ketoprofen-derived thiazolidin-4-one hybrids, particularly AR3 and AR1, merit further investigation as potential anti-inflammatory agents, with AR3 prioritized mainly by in vivo activity and AR1 supported by computational evidence.

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DOI: 10.3897/pharmacia.73.e201921

Authors: Ivalina Valchinkova, Ivanka Kostadinova

Abstract: This study investigated the effects of creatine monohydrate (CrM, 1.5 g/kg/day); newly synthesized creatine lysinate (CrLys), creatine leucinate (CrLeu), creatine isoleucinate (CrIsoleu), creatine arginate (CrArg), and creatine valinate (CrVal) at a dose of 5 g/kg/day; and the antidepressants citalopram and fluoxetine at a dose of 20 mg/kg in the passive avoidance test, rotarod test, and tail suspension test (TST). After 2 weeks of peroral administration in mice, an increase in latency time in the passive avoidance test was observed in the groups treated with CrLeu and fluoxetine. In the rotarod test, the group that received CrIsoleu reached better outcomes on day 14 compared to the other groups. A slight decrease in immobility time in the TST was observed in the groups treated with CrM, CrLys, and fluoxetine. Based on the current results, supplementation with CrM, CrLys, CrLeu, and CrIsoleu shows promise in improving physical and cognitive performance in mice.

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DOI: 10.3897/pharmacia.73.e186370

Authors: Abeer Kharshid, Omar Alasasfeh, Mohammad Saleh, Adham Halasah, Shahed Amran Alsulman, Rana Alfaqeer, Renad Tarawneh, Dima Alhawarneh, Forat Maaitah, Mohammad Alkfaween

Abstract: The growth of autonomous artificial intelligence (AI) systems for diabetic retinopathy screening and conversational AI tools for glaucoma management has the potential to substantially enhance community pharmacy practice. However, limited evidence exists regarding the real-world use and integration of these technologies. This study assessed the effectiveness of pharmacist-facilitated AI-driven diabetic retinopathy (DR) screening on screening uptake and referral completion and evaluated the effect of a pharmacist-supervised large language model (LLM) chatbot on medication adherence and intraocular pressure (IOP) in patients with primary open-angle glaucoma. A pragmatic 6-month study (July through December 2024) was conducted in four community pharmacies in Al-Karak, Jordan. Phase 1 included adults with diabetes receiving AI-assisted fundus photography (AEYE-DS), whereas Phase 2 randomized glaucoma patients to receive either text-message reminders or pharmacist-supported chatbot interactions using WhatsApp (GPT-4). In Phase 1, 402/518 participants (77.6%) completed screening; 16.9% needed referral, and 81.0% attended ophthalmology visits. The chatbot group in Phase 2 (n = 94) showed improved medication possession ratio (MPR) adherence (MPR 0.91 ± 0.06 vs. 0.79 ± 0.11; p < 0.001), fewer missed doses (3.2 ± 2.1 vs. 7.0 ± 3.4; p = 0.002), and greater reductions in IOP (2.8 ± 3.6 vs. 0.9 ± 4.1 mmHg; p = 0.010). These results indicate that the integration of AI-based services into community pharmacy care may be beneficial.

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DOI: 10.3897/pharmacia.73.e186971

Authors: Mohammed R. Abdulmonem, Monther F. Mahdi, Ayad M. R. Raauf

Abstract: Targeted therapy has improved the management of non-small cell lung cancer (NSCLC); however, resistance and suboptimal responses persist, requiring the development of new epidermal growth factor receptor (EGFR)-directed chemotypes. A series of benzohydrazide derivatives (3a–f) was synthesized and characterized using FT-IR, 1H NMR, and 13C NMR. In silico ADME profiling predicted high oral absorption for the series and acceptable MW/HBD/HBA ranges; however, the elevated predicted lipophilicity (QPlogPo/w > 5) suggested potential solubility and nonspecific binding risks. Compound 3e had the most balanced size and polarity profile, and compound 3f had the highest predicted permeability. Binding was evaluated against two EGFR kinase conformations (PDB: 1M17, active-like; 4HJO, inactive-like) using /native-ligand redocking, docking/induced-fit docking, Prime MM-GBSA, and 200 ns molecular dynamics simulations, together with three EGFR reference inhibitors and five DUD-E decoys. The docking/MM-GBSA results suggested conformation-dependent binding, with 3d favored in 1M17 and 3f in 4HJO, with recurrent ATP-site contacts. Overall, these compounds represent computationally prioritized EGFR-directed scaffolds for experimental validation rather than confirmed EGFR inhibitors.

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DOI: 10.3897/pharmacia.73.e195774

Authors: Denitsa Stefanova, Yavor Mitkov, Virginia Tzankova

Abstract: The effects of a series of caffeine-8-α-methylthioglycolic acid derivatives (Jas 1–Jas 10), possessing potential applicability in neurodegenerative diseases, were investigated using neurotoxicity models based on the human neuroblastoma cell line SH-SY5Y. These compounds contain various substituents that modify and improve the physicochemical properties of caffeine, including solubility, molecular weight, and acidity, which may influence their biological activity. The proposed mechanism of action is associated with the modulation of G protein-coupled adenosine receptors in neuronal cells. The neuroprotective potential of the compounds was evaluated in an L-glutamate (L-GLU, 60 mM, 24 h)-induced excitotoxicity model and hydrogen peroxide (H2O2, 5 μM and 6 μM, 1 h)-induced oxidative stress models. Cell viability and intracellular reactive oxygen species (ROS) production were analyzed using standard in vitro assays. The results demonstrated that the tested derivatives exhibited antioxidant and moderate neuroprotective effects in both experimental models. The most pronounced activity was observed for compound Jas 9 in the L-GLU-induced neurotoxicity model and for compound Jas 8 in the H2O2-induced oxidative stress model. Furthermore, Jas 8 statistically significantly reduced intracellular ROS production (+++p < 0.001), supporting its strong antioxidant potential. Overall, these findings indicate that the selected caffeine derivatives are promising candidates for further pharmacological and toxicological evaluation.

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DOI: 10.3897/pharmacia.73.e189281

Authors: Magdalena Kondeva-Burdina, Elina Bacheva, Javor Mitkov

Abstract: The defining neuropathological features of Parkinson’s disease (PD) include the progressive loss of dopaminergic neurons in the substantia nigra, together with the intraneuronal accumulation of α-synuclein in the form of Lewy bodies. Theobromine has been shown to possess neuroprotective effects, preventing neuronal damage, enhancing motor memory and cognitive function in humans (Gao et al. 2022). Bhat et al. (2021) demonstrated the neuroprotective effects of theobromine in a rat model of transient global cerebral ischemia/reperfusion (tGCI/R). The study of Haj Ahmed et al. (2020) investigated the interaction between several methylxanthines and primary amine oxidase (PrAO)/ monoamine oxidase (MAO) in human subcutaneous adipose tissue (hScAT). Caffeine and theobromine produced a remarkable 50% inhibition of PrAO activity when incubated at 2.5 mM with hScAT. Due to its low side-effect profile and minimal toxicity at appropriate doses, theobromine and its derivatives are considered promising agents for the prevention of neurological disorders, offering potential applications in medicine.

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DOI: 10.3897/pharmacia.73.e197010

Authors: Maria Kokudeva, Tsvetelina Velikova, Georgi Momekov

Abstract: The COVID-19 pandemic precipitated unprecedented global efforts to repurpose existing pharmacotherapeutic agents, yet the translation of emerging evidence into clinical practice revealed critical systemic failures. This study presents a living systematic review and network meta-analysis of randomized controlled trials evaluating hydroxychloroquine, chloroquine, ivermectin, azithromycin, and doxycycline through December 2022 using the COVID-NMA database. Pooled analyses demonstrated no statistically significant efficacy for any evaluated drug across outpatient and inpatient settings. Hydroxychloroquine showed no mortality benefit (risk ratio 1.08, 95% confidence interval 0.97–1.19; 16 trials, N = 15,000). Ivermectin demonstrated no effect on hospitalization (risk ratio 0.90, 95% confidence interval 0.70–1.16). Azithromycin showed no benefit in clinical improvement (risk ratio 1.02, 95% confidence interval 0.99–1.05). International guidelines converged on strong recommendations against these agents by late 2021. In contrast, Bulgaria—a critical case study with the European Union’s highest COVID-19 mortality, lowest healthcare spending, and profound institutional distrust—exhibited persistent evidence–practice gaps: 70% of patients received unnecessary antibiotics, antimicrobial consumption surged by 27%, and carbapenem resistance in Klebsiella pneumoniae reached 40.6%. The failure of drug repurposing strategies stemmed not from insufficient scientific evidence but from systemic breakdowns in evidence translation mechanisms. These findings underscore the necessity of pre-positioned platform trials, embedded antimicrobial stewardship, and trust-building infrastructure for future pandemic preparedness.

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DOI: 10.3897/pharmacia.73.e168282

Authors: Tsvetelina Velikova, Antoaneta Mihova, Hassan Ali, Adriana Angelova, Verginiya Ivanova, Eugeni Pentchev, Rosen Mihaylov, Blagovesta Pencheva

Abstract: Background: Recurrent infections in children may occur despite normal baseline immune function, highlighting the need for targeted immunomodulatory interventions. Prior use of other immunomodulators, such as bacterial lysates and beta-glucans, can influence immune parameters and should be considered when interpreting treatment effects. Objective: To evaluate the short-term effects of inosine acedoben dimepranol (IAD) on immune cell subsets and activation markers in two pediatric patients with recurrent infections. Methods: Two children aged 3 years with frequent infections but normal routine immunological screening were treated with IAD for a brief 7-day period as part of a broader adjunctive immunotherapy regimen, including other immunomodulators. Comprehensive immunophenotyping of T, B, and natural killer (NK) cells, as well as subset-specific naïve, memory, and activation markers (CD38, CD25, and HLA-DR), was performed before and after therapy using flow cytometry. Results: Baseline analysis revealed distinct immune dysregulation patterns: B-cell predominance in one patient and T-cell, mainly CD4+, expansion in the other, accompanied by evidence of chronic immune activation. Following short-term IAD administration, both patients demonstrated case-specific, transient immunological changes, including partial normalization of naïve CD4+ T-cell proportions, reduction of some activation markers, and modest changes in memory B-cell subsets. Absolute lymphocyte counts and subset dynamics were consistent with short-term clinical observations. No adverse effects were observed during treatment. Conclusion: Short-term IAD therapy was associated with preliminary, case-specific modulation of lymphocyte compartments and partial attenuation of chronic immune activation. Given the brief duration and concurrent use of other immunomodulators, these findings should be interpreted cautiously. Nevertheless, detailed immunophenotyping can provide valuable insights to guide individualized adjunctive immunomodulatory therapy in pediatric patients.

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