European Journal of Clinical Pharmacology最新文献

{"title":"Signals from randomized clinical trials predicting hepatotoxicity of flupirtine: systematic review.","authors":"Mahir Fidahic, Emilija Lozo Vukovac, Ewa Balkowiec-Iskra, Darko Krnic, Adriana Andric, Zeljana Margan Koletic, Livia Puljak","doi":"10.1007/s00228-025-03840-8","DOIUrl":"https://doi.org/10.1007/s00228-025-03840-8","url":null,"abstract":"<p><strong>Background: </strong>The aim of this study was to systematically review clinical trials evaluating the flupirtine to identify any biochemical or clinical indicators that could signal serious hepatotoxicity.</p><p><strong>Methods: </strong>This systematic review included randomized controlled trials (RCTs) evaluating flupirtine-containing medicines for any clinical condition. Trials involving any population, comparator, or outcome were considered eligible for inclusion. A comprehensive search was conducted in Embase, MEDLINE, and CENTRAL from their inception until August 14, 2023. The risk of bias (RoB) in the included trials was assessed using Cochrane's 2011 RoB tool. Due to the heterogeneity of the included trials, a meta-analysis could not be performed.</p><p><strong>Results: </strong>A total of 35 trials published between 1983 and 2022 were included in this systematic review, with 1408 participants receiving flupirtine. Only five trials reported any data related to liver function tests. Among these, four trials documented transient, asymptomatic liver abnormalities that returned to normal after the trial period, while one trial was prematurely terminated. One trial reported normal liver test results in all participants. Of the three trials published after 2018, only one acknowledged the withdrawal of flupirtine from the European market. The majority of risk of bias (RoB) domains were classified as having an unclear risk of bias.</p><p><strong>Conclusion: </strong>Published RCTs did not report any evidence of serious hepatotoxicity associated with flupirtine based on the available biochemical or clinical data. However, liver function test results were reported in only 5 out of 35 included trials. Published RCTs are not reliable information about flupirtine-related hepatotoxicity.</p><p><strong>Registration: </strong>Protocol was published in PROSPERO (CRD42018085123).</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post-market safety profile and suicide/self-injury risk signals of dextromethorphan/bupropion: a real-world pharmacovigilance study.","authors":"Lingjing Yuan, Jianping He, Xiangyu Li","doi":"10.1007/s00228-025-03841-7","DOIUrl":"https://doi.org/10.1007/s00228-025-03841-7","url":null,"abstract":"<p><strong>Background: </strong>Dextromethorphan/bupropion (D/B) is an innovative pharmacological treatment for major depressive disorder. Nevertheless, the current evidence regarding the safety profile of D/B is predominantly derived from clinical trials, thus hindering the timely updating of adverse event (AE) data for this medication. Therefore, this study conducted data mining and analysis of AE signals (especially for suicide/self-injury) associated with D/B using the Food and Drug Administration Adverse Event Reporting System (FAERS) database.</p><p><strong>Methods: </strong>This study used the disproportionality method to systematically evaluate the associations between D/B and potential AEs and compared these AEs with AEs related to bupropion and esketamine by using data from the FAERS collected between the third quarter of 2022 and the second quarter of 2024.</p><p><strong>Results: </strong>A total of 2451 AE reports identifying D/B as the \"primary suspect\" were collected. From these reports, 81 preferred terms and 24 system organ classifications were identified, with a predominant focus on psychiatric disorders (22.07%) and nervous system disorders (18.77%). These AEs were mostly found in individuals aged 18-44 years. The median time to onset for D/B-related AEs was determined to be 2 days. Nearly 20 novel AEs identified during the labelling process were detected, such as a sensation of inebriation and panic attacks. Importantly, the risk signals for suicide/self-injury associated with D/B were significantly lower than those associated with bupropion and esketamine. However, these signals cannot be ignored in view of their serious consequences.</p><p><strong>Conclusion: </strong>Psychiatric and nervous system disorders, such as suicidal/self-injurious behaviours, require careful monitoring in clinical applications. It is imperative to conduct traditional pharmacoepidemiological research to evaluate whether D/B is linked to an increased risk of dissociative disorders in the future. Moreover, health care professionals should remain vigilant for AE signals not listed in package inserts.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of a medication discrepancy management platform in reducing medication discrepancy and influencing factors among elderly patients with polypharmacy.","authors":"Jingyan Song, Jie Huang, Jian Mao, Jing Cao, Qinghua Zhao","doi":"10.1007/s00228-025-03831-9","DOIUrl":"https://doi.org/10.1007/s00228-025-03831-9","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the impact of a medication discrepancy management platform on reducing medication discrepancies among elderly patients with polypharmacy and to analyze influencing factors.</p><p><strong>Methods: </strong>A total of 110 elderly polypharmacy patients were divided into a control group and an observation group using a random number method, each with 55 participants. The control group received routine management, while the observation group utilized a medication discrepancy management platform. Medication knowledge and adherence before and after intervention were compared between the two groups. Reasons and types of medication discrepancies were statistically analyzed. Patients were divided into a non-discrepancy group and a discrepancy group, with multivariate logistic regression used to analyze factors influencing medication discrepancies among elderly patients with polypharmacy.</p><p><strong>Results: </strong>Utilizing a medication discrepancy management platform significantly improved medication knowledge and adherence among elderly patients (P < 0.05). A total of 34 patients (30.91%) experienced at least one medication discrepancy within one-week post-discharge, primarily involving decreased frequency, missed doses, reduction in medication types, and medication substitution. Multivariate logistic regression analysis showed that the use of the medication discrepancy management platform, caregiver involvement, and prescribed discharge medications (7-8 types or ≥ 9 types) were independent factors influencing medication discrepancies in elderly patients (P < 0.05).</p><p><strong>Conclusion: </strong>Using a medication discrepancy management platform can effectively reduce medication discrepancies in elderly patients with polypharmacy and improve elderly patients' adherence to medication. Expanding the platform's use can enhance discharge guidance quality and ensure medication safety.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the editor: Relevant errors in a systematic review and network meta-analysis evaluating the efficacy and safety of different pharmacological interventions in the treatment of tardive dyskinesia.","authors":"Christoph U Correll, David Rowe, Rinat Ribalov, Verena Ramirez Campos, Marco Solmi","doi":"10.1007/s00228-025-03826-6","DOIUrl":"https://doi.org/10.1007/s00228-025-03826-6","url":null,"abstract":"","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical pharmacology-how it shapes the drug development journey.","authors":"Matthias Kruse, Simona Stankeviciute, Sheryl Perry","doi":"10.1007/s00228-025-03811-z","DOIUrl":"10.1007/s00228-025-03811-z","url":null,"abstract":"<p><p>Every drug development is a complex and long journey. Clinical pharmacology is an essential discipline in modern drug development. With its applications, computational modelling, and simulation techniques, it can significantly contribute to the efficiency in drug development today. In this perspective, we highlight why pharmacokinetics and pharmacodynamics are important, what developers need to consider in their clinical development programme, how modelling influences the development process, and discuss recent trends such as artificial intelligence and machine learning that have the potential to reshape future drug development.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"597-604"},"PeriodicalIF":2.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11922982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk of hospital inpatient opioid overdose (RHINOO): a review of factors impacting naloxone administration in patients receiving opioids.","authors":"Heather Alban, Natasha Ireifej, John D'Alessandro, Garrett Jordan, Ryan Lee, Nicholas Patricia, Jill Stoltzfus, Auguste Niyibizi","doi":"10.1007/s00228-025-03801-1","DOIUrl":"10.1007/s00228-025-03801-1","url":null,"abstract":"<p><strong>Purpose: </strong>Opioid medications remain a common treatment for acute pain in hospitalized patients. This study aims to identify factors contributing to opioid overdose in the inpatient population, addressing the gap in data on which patients are at higher risk for opioid-related adverse events in the hospital setting.</p><p><strong>Methods: </strong>A retrospective chart review of inpatients receiving at least one opioid medication was performed at a large academic medical center from January 1, 2022, through December 31, 2022. Patients who received naloxone were designated as the overdose group, while those who received opioids without naloxone served as the control group. Suspected risk factors were included in a multivariable direct logistic regression model to identify patients at higher risk for opioid-related adverse events.</p><p><strong>Results: </strong>The review included 11,050 admitted patients who received an inpatient opioid, of whom 130 received naloxone. Analysis revealed that patients with creatinine clearance (CrCl) < 60 mL/min, co-administered benzodiazepine, body mass index (BMI) > 30 kg/m², underlying pulmonary disease, obstructive sleep apnea, chronic opioid use, and/or substance use disorder were at higher risk for requiring naloxone. These factors significantly influenced the likelihood and magnitude of in-hospital opioid overdose.</p><p><strong>Conclusion: </strong>These validated risk factors should be considered when administering opioid analgesics in the inpatient setting. Consideration should be given to reducing the dose and/or frequency of opioids in addition to the use of alternative analgesic modalities for patients with these risk factors to mitigate the risk of opioid-related adverse events. Incorporating these considerations into clinical practice can enhance patient safety and outcomes.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"543-550"},"PeriodicalIF":2.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adjunctive treatment for pediatric focal epilepsy: a systematic review.","authors":"Siru Wang, Hu Sun, Zhaoxuan Wang, Chunxiao Sun, Xiaolu Zhang, Chang Liu","doi":"10.1007/s00228-025-03807-9","DOIUrl":"10.1007/s00228-025-03807-9","url":null,"abstract":"<p><strong>Purpose: </strong>We aim to use a network meta-analysis to evaluate the efficacy and safety of antiseizure medications and provide a theoretical basis for rational drug use for children and adolescents in adjunctive treatment.</p><p><strong>Methods: </strong>The databases of PubMed, Embase, Cochrane Library, and Web of Science were systematically searched for random clinical trials about perampanel, valproic acid, carbamazepine, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, topiramate, zonisamide, brivaracetam, cenobamate, eslicarbazepine acetate, and pregabalin from their inception until December 10, 2023. The included studies' risk of bias was evaluated by the Cochrane Collaboration's tool (RoB2). The network meta-analysis was performed using Stata 15 on the included studies.</p><p><strong>Results: </strong>Seventeen studies were identified and of these 19 randomized controlled trials evaluating 9 different antiepileptic drugs were included. In total, 2959 patients were covered in the analysis of the outcomes. For efficacy, lacosamide (OR = 1.91, 95%CI 1.14-3.20), lamotrigine (OR = 3.82, 95%CI 1.86-7.83), levetiracetam (OR = 3.01, 95%CI 1.89-4.80), oxcarbazepine (OR = 2.75, 95%CI 1.52-4.96), perampanel (OR = 2.05, 95%CI 1.15-3.65), and zonisamide (OR = 2.27, 95%CI 1.21-4.24) were more effective than placebo in the 50% responder rate. Lamotrigine ranked first on the cumulative probability curve, followed by levetiracetam. Eslicarbazepine acetate (OR = 6.44, 95%CI 1.43-29.00) and levetiracetam (OR = 5.75, 95%CI 2.45-13.50) were better than placebo in seizure freedom. For safety, topiramate (OR = 4.11, 95%CI 1.43-11.76) and oxcarbazepine (OR = 2.72, 1.28-5.76) were more likely to cause adverse effects in children or adolescents compared to placebo.</p><p><strong>Conclusion: </strong>In terms of efficacy and safety, lamotrigine and levetiracetam may be selected preferentially for the adjunctive treatment of focal epilepsy in children and adolescents. However, owing to the limited random clinical trials, our results need to be verified by further studies.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"507-523"},"PeriodicalIF":2.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of metoprolol exposure following myocardial infarction on future cardiovascular events: a Mendelian randomization study.","authors":"Lina Dorthea Bruun, Geir Øystein Andersen, Marianne Kristiansen Kringen, Peder Langeland Myhre, Sigrun Halvorsen, Charlotte Holst Hansen, Espen Molden, Erik Øie","doi":"10.1007/s00228-025-03806-w","DOIUrl":"10.1007/s00228-025-03806-w","url":null,"abstract":"<p><strong>Purpose: </strong>The clinical benefit of up-titration of metoprolol to a guideline-recommended target dose after myocardial infarction (MI) is unknown. Our aim was to investigate whether variation in metoprolol exposure determined by cytochrome p450 enzyme 2D6 (CYP2D6) influences the occurrence of major adverse cardiovascular events (MACE) and cardiovascular death (CV death) among patients treated with metoprolol after MI.</p><p><strong>Method: </strong>This Mendelian randomization study was performed using individual-level data from 1554 patients treated with metoprolol after an acute MI. CYPD26 genotype was applied as a binary genetic instrument assigning patients into two metoprolol exposure groups: CYP2D6 normal metabolizers (NM) (low exposure) and CYP2D6 intermediate and poor metabolizers (IM + PM) (high exposure). The null hypothesis of no association between the CYP2D6 metabolizer subgroup and MACE or CV death was tested using the Cox proportional hazards model. All-cause mortality and individual components of MACE were included as secondary outcomes.</p><p><strong>Results: </strong>In total, 879 (56.6%) patients were classified as NM and 675 (43.4%) as IM + PM. During the 3-year follow-up, 56 patients (6.4%) in the NM group had an outcome of MACE, and 24 (2.7%) patients died from CV disease. Corresponding frequency in the IM + PM group was 47 (7.0%) and 22 (3.3%), respectively. There was no association between genotype and MACE [unadjusted HR 1.12 (CI 0.76, 1.65)] or CV death [unadjusted HR 1.20 (CI 0.67, 2.14)], or between the CYP2D6 group and any of the secondary outcomes.</p><p><strong>Conclusion: </strong>In patients treated with metoprolol after MI, variation in metoprolol exposure determined by CYP2D6 did not impact the occurrence of cardiovascular events.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"551-560"},"PeriodicalIF":2.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11923007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disproportionality analysis from World Health Organization data on migraine-specific medications and cerebrovascular diseases.","authors":"Jaehyeong Cho, Hyesu Jo, Jaeyu Park, Kyeongmin Lee, Hayeon Lee, Soeun Kim, Yejun Son, Jeongseon Oh, Jinyoung Jeong, Sooji Lee, Jiyeon Oh, Hanseul Cho, Jee Myung Yang, Ho Geol Woo, Dong Keon Yon, Lee Smith","doi":"10.1007/s00228-025-03812-y","DOIUrl":"10.1007/s00228-025-03812-y","url":null,"abstract":"<p><strong>Background: </strong>Migraine is a major cause of population ill health, with an estimated global prevalence of approximately 14-15%. However, given the limited research on the associations between specific migraine medications and adverse cerebrovascular events, this study aimed to investigate these relationships and their impact on cerebrovascular risk.</p><p><strong>Methods: </strong>This study utilized data from the global pharmacovigilance database, which covers 170 countries from 1968 to 2024. We examined the reporting frequency of adverse cerebrovascular events with 10 migraine medications, with analysis stratified by sex and age. The information component (IC) was calculated using a Bayesian method, while the reporting odds ratio (ROR) was calculated using a frequentist approach to compare reported versus non-reported outcomes.</p><p><strong>Results: </strong>Among the more than 140 million adverse drug events, 6,080 cases were identified as adverse cerebrovascular events associated with migraine-specific medications. Significant associations with cerebrovascular diseases were observed in both males (ROR, 1.24 [95% CI, 1.19-1.30]; IC 0.31 [IC_0.25, 0.24]) and females (1.73 [1.67-1.79]; 0.78 [0.72]), with most age groups showing significance, except for those 75 years and older. Among the 10 medication categories, 6 categories were associated with adverse cerebrovascular diseases: CGRP antagonists (ROR, 1.22 [95% CI, 1.12-1.33]; IC, 0.28 [IC_0.25,0.14]), ergot alkaloids (3.66 [2.97-4.51]; 1.84 [1.49]), 5-HT₁ receptor agonists (3.33 [2.97-4.51]; 1.72 [1.59]), beta-blockers (2.03 [1.94-2.13]; 1.02 [0.94]), calcium channel blockers (1.46 [1.30-1.64]; 0.54 [0.34]), and clonidine (2.18 [2.04-2.33]; 1.11 [1.00]).</p><p><strong>Conclusion: </strong>This study found that commonly used migraine medications are significantly associated with an increased risk of cerebrovascular diseases, highlighting the need for careful patient evaluation and selection.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"571-581"},"PeriodicalIF":2.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Considerations of sex in bioequivalence assessments: does sex affect pharmacokinetic variability between evaluation formulations?","authors":"Ji-Hun Jang, Seung-Hyun Jeong","doi":"10.1007/s00228-025-03813-x","DOIUrl":"10.1007/s00228-025-03813-x","url":null,"abstract":"<p><strong>Background: </strong>Bioequivalence assessment determines the equivalence between drug formulations and is primarily used to demonstrate that a generic product is equivalent to its reference. The sex of the drug consumer is a major consideration in bioequivalence assessment, but specific ratios or absolute criteria for sex composition are usually not specified.</p><p><strong>Purpose: </strong>This study explored whether the sex of participants in a bioequivalence assessment could significantly affect the pharmacokinetic variability between formulations and decision outcomes. In bioequivalence studies, the sex composition should reflect the drug's target population, but it is often acceptable to limit it to healthy adult males. Therefore, it is essential to consider the variation in bioequivalence results according to sex.</p><p><strong>Methods: </strong>Levocetirizine and rabeprazole enteric-coated tablets were chosen as investigational agents, and clinical trial data for these were used in the bioequivalence analysis. This analysis was conducted both with and without considering sex, and the final determination of equivalence was based on whether the 90% confidence interval for the ratio of standard pharmacokinetic parameters between the reference and test formulations fell within the 80 to 125% range. Additionally, principal component analysis (PCA) was performed to determine whether there were significant differences in the targeted pharmacokinetic parameter values between drug formulations across each sex group.</p><p><strong>Results: </strong>Bioequivalence of levocetirizine's reference and test formulations was confirmed, independent of sex. For rabeprazole, bioequivalence was established in males-even without considering sex-but not in females, based on extended criteria for drugs with significant pharmacokinetic variability. The PCA results also showed that there were significant differences (P < 0.05) in the distribution of pharmacokinetic parameters of rabeprazole by gender and formulation. This indicates that equivalence assessments may vary based on pharmacokinetic differences related to sex among subjects in bioequivalence studies. Thus, it was shown that sex may influence pharmacokinetic variability between reference and test formulations of the same drug.</p><p><strong>Conclusion: </strong>This study provided valuable insights into the role of sex in bioequivalence studies. For drugs exhibiting significant pharmacokinetic differences between sexes, it is crucial to recognize that bioequivalence results may vary based on the sex ratio in the participant group. Therefore, further analysis and interpretation, taking sex-related factors into account, will be necessary during bioequivalence evaluations.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"583-596"},"PeriodicalIF":2.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143498956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}