European Journal of Clinical Pharmacology最新文献

{"title":"External validation of population pharmacokinetic models of oxcarbazepine active metabolite in Chinese children with epilepsy.","authors":"Ruoyun Wu, Xintian Li, Yujie Wu, Zhigang Zhao, Weixing Feng, Shenghui Mei","doi":"10.1007/s00228-025-03875-x","DOIUrl":"10.1007/s00228-025-03875-x","url":null,"abstract":"<p><strong>Objective: </strong>To assess the predictive performance of published population pharmacokinetic models of the oxcarbazepine (OXC) active metabolite, 10, 11-dihydro-10-monohydroxycarbazepine (MHD), using external data sets in Chinese children with epilepsy.</p><p><strong>Method: </strong>A total of 231 concentrations from 185 Chinese children with epilepsy were used for external validation. PubMed, Embase, and Web of Science were searched for published PPK models of OXC active metabolite MHD in children. Seven models were searched and labeled A to G based on the year of publication. Prediction error, visual predictive check, and normal prediction distribution error tests were employed to assess the model's extrapolation performance. The Bayesian prediction method was applied to ascertain the influence of prior concentrations on the model's predictive performance.</p><p><strong>Result: </strong>A total of seven MHD PPK models were retrieved. Models A, D, E, and G exhibited good predictive performance in prediction-based diagnostics and visual predictive checks. The normalized predictive distribution error test shows that none of the models is suitable to describe our data. Bayesian prediction significantly improved the prediction performance of all the models with one prior observation.</p><p><strong>Conclusion: </strong>The published MHD PPK models showed extensive variation in predictive performance when extrapolated in Chinese children with epilepsy. Bayesian forecasting substantially improved the predictive performance of the model and might facilitate the customization of OXC dosing.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"1439-1449"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706791","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":"Possible increased risks of cholecystitis in patients with idiopathic pulmonary fibrosis treated with nintedanib.","authors":"Catherine Kiani, Alexandre Bleinc, Theodora Bejan-Angoulvant, Marion Teulier, Sylvain Marchand-Adam","doi":"10.1007/s00228-025-03867-x","DOIUrl":"10.1007/s00228-025-03867-x","url":null,"abstract":"","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"1533-1535"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12443869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689653","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":"Study on disproportionality in the detection of potential signals between quetiapine and diabetic ketoacidosis.","authors":"Haiya Liang, Dandan Mao, Yan Zhao, Rongjing Zhou","doi":"10.1007/s00228-025-03895-7","DOIUrl":"10.1007/s00228-025-03895-7","url":null,"abstract":"<p><strong>Purpose: </strong>Quetiapine is an atypical second-generation antipsychotic. Diabetic ketoacidosis (DKA) is an acute metabolic complication, most commonly encountered in type 1 diabetes, and it can be life-threatening if not treated promptly. This study aimed to assess quetiapine-associated DKA using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database.</p><p><strong>Methods: </strong>We performed a retrospective investigation on the FAERS from the first quarter of 2004 to the second quarter of 2024 using the reporting odds ratio (ROR) and proportional reporting ratio (PRR) from the disproportionality analysis. According to the Medical Dictionary for Regulatory Activities (MedDRA) 26.1, preferred terms (PTs) of reports on adverse drug reactions (ADRs) were classified using System Organ Classification (SOC), and filtered based on hyperglycemia and new-onset diabetes mellitus in the Standardized MedDRA Query (SMQ).</p><p><strong>Results: </strong>We collected 65,536 ADR reports with quetiapine as the primary suspected drug, including 27 system organ classifications. There were 3,046 cases related to DKA, predominantly from the United States, with a slightly higher proportion of females (51.31%) than males (45.63%). The most common severe ADR outcome (539 cases, 17.70%) was hospitalization-initial or prolonged, followed by death (333 cases, 10.93%). Additionally, compared to the other three second-generation antipsychotics (clozapine, olanzapine, and risperidone), quetiapine exhibited a stronger association with DKA (ROR = 31.05, ROR025 = 29.87).</p><p><strong>Conclusion: </strong>Quetiapine could be associated with DKA; therefore, physicians should be aware of this potentially fatal adverse event. Studies are needed to investigate the matter further.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"1473-1479"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728939","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":"Benchmarking non-inferiority design and analysis through the Z-score.","authors":"Jin Wang","doi":"10.1007/s00228-025-03877-9","DOIUrl":"10.1007/s00228-025-03877-9","url":null,"abstract":"<p><strong>Purpose: </strong>Non-inferiority (NI) design and analyses are frequently employed to provide alternative therapy options to patients, ensuring these therapies are not significantly worse in terms of safety and effectiveness compared to the standard therapy. However, unlike superiority analysis, non-inferiority analysis faces the inherent challenge of a potentially irrelevant NI margin. It is not uncommon for the observed control performance to differ significantly from the assumed one, which can render the NI margin irrelevant. The purpose of this paper is to utilize Z-score to investigate this issue.</p><p><strong>Methods: </strong>This paper proposes using the Z-score to evaluate the NI design and connect the NI design and analysis. This approach provides a benchmark tool that even when actual outcomes differ significantly from assumptions, the NI margin can be moderated to balance clinical relevance and statistical practicality.</p><p><strong>Results: </strong>Illustrative calibrations and case studies demonstrate the feasibility of this approach, facilitating the transition from NI design to analysis.</p><p><strong>Conclusion: </strong>The Z-score can be used to assess the quality of the NI design and serve as a bridge between NI design and analysis.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"1421-1427"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658758","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":"Pharmacogenetics and pharmacometabolomics predictors of clozapine and norclozapine pharmacokinetic exposure in healthy volunteers.","authors":"Orwa Albitar, Mohd Rahimi Muda, Siti Maisharah Sheikh Ghadzi, Dzul Azri Mohamed Noor, Baharudin Ibrahim, Chin-Hoe Teh, Mohammed Ahmed Akkaif, Fatimatuzzahra' Abd Aziz","doi":"10.1007/s00228-025-03884-w","DOIUrl":"10.1007/s00228-025-03884-w","url":null,"abstract":"<p><strong>Purpose: </strong>Clozapine is the only effective medication for unresponsive schizophrenia. However, it has a complicated dose-concentration relationship. The present study aimed to investigate the role of some genetic polymorphisms and metabolic profiles in addressing the variability in clozapine and norclozapine concentrations.</p><p><strong>Methods: </strong>A single dose of 12.5 mg clozapine was administered to 33 healthy volunteers, from whom 270 samples were collected at 30 min, 1, 2, 3, 5, and 8 h. The concentrations of clozapine and norclozapine were determined using HPLC-UV. CYP1A2 -163 C>A, ABCB1 3435 C>T, and ABCB1 2677 G>T genetic polymorphisms were investigated using allele-specific polymerase chain reaction and restriction fragment length polymorphism, and the metabolic profiles were identified using proton nuclear magnetic resonance (¹H NMR).</p><p><strong>Results: </strong>Clozapine concentrations and area under the curve (AUC) were higher, and the clearance was 38.3% (95% confidence intervals (95% CI), 4.5-72.2%) lower in the CYP1A2 -163 AA genotype, while clozapine initial concentrations were lower in the ABCB1 2677 GG genotype. In a multiple regression analysis, glucose (p-value, 0.009) was significantly associated with the norclozapine to clozapine AUC (N:C) ratio.</p><p><strong>Conclusions: </strong>Variabilities in clozapine pharmacokinetics were accounted for using genetic polymorphisms and metabolic profiles. Clozapine concentrations in CYP1A2 -163 C>A polymorphism should be cautiously interpreted considering the smoking status. Altered glucose levels, besides being an adverse effect of clozapine, may also be indirectly associated with variability in CYP1A2 activity as indicated by the N:C ratio to be confirmed in larger and controlled trials.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"1429-1438"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689652","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":"Cost-effectiveness of abortive and preventative treatments in patients with migraine: a systematic review.","authors":"Arefe Rashidi, Mohammadreza Keramati, Hadi Esmaily, Maryam Talebi, Ghader Mohammadnezhad","doi":"10.1007/s00228-025-03881-z","DOIUrl":"10.1007/s00228-025-03881-z","url":null,"abstract":"<p><strong>Background: </strong>Migraine imposes significant personal, societal, and economic burdens globally. Both abortive and preventative medications have evolved, yet their economic implications require further exploration, particularly for high-cost novel therapies such as calcitonin gene-related peptide (CGRP) inhibitors. This systematic review evaluates the cost-effectiveness of migraine interventions, focusing on both abortive and preventive interventions across diverse healthcare settings.</p><p><strong>Methods: </strong>A systematic review was conducted to evaluate economic evaluations of migraine treatments published between 2014 and 2024. Inclusion criteria comprised full economic evaluations reporting incremental cost-effectiveness ratios (ICERs) and quality-adjusted life years (QALYs). Data extracted included country settings, perspectives, interventions compared, real-world data sources or economic models, and key outcomes.</p><p><strong>Results: </strong>Of the 2172 unique records screened, 20 eligible peer-reviewed studies were included. Recent studies have focused on CGRP inhibitors, especially erenumab. However, BTX, anticonvulsants, surgery, simple analgesics, triptans, medical devices, and direct-site anesthetic/glucocorticoid injections are still discussed in some contexts. CGRP inhibitor monoclonal antibodies demonstrated ICERs ranging from 50,000 to 250,000 USD/QALY in high-income countries but often exceeded willingness-to-pay (WTP) thresholds in lower-resource settings. Preventive modalities like BTX were cost-effective for chronic migraine, with ICERs of 30,000-70,000 USD/QALY. Sensitivity analyses revealed that drug costs, adherence, and discount rates significantly influenced results.</p><p><strong>Conclusion: </strong>Economic evaluations underscore the clinical benefits of novel migraine therapies but reveal price challenges, particularly in resource-limited settings. Biosimilar adoption and head-to-head cost comparisons are essential to improving access. Tailoring migraine management strategies to regional economic contexts remains critical to achieving sustainable and equitable care.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"1381-1399"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636511","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":"The effects of trazodone exposure during pregnancy on fetal outcomes: a systematic review.","authors":"Britney Glasgow-Osment, Farah Wahib, Shama Kassam, Madeleine Zanin, Facundo Garcia-Bournissen","doi":"10.1007/s00228-025-03880-0","DOIUrl":"10.1007/s00228-025-03880-0","url":null,"abstract":"<p><strong>Purpose: </strong>Trazodone, a medication primarily used for anxiety and insomnia, is increasingly prescribed during pregnancy despite limited safety data. This systematic review aims to assess the effects of trazodone exposure during pregnancy on fetal outcomes.</p><p><strong>Methods: </strong>A search was conducted using MEDLINE and Embase databases from the year 2000 to present. Studies were limited to those involving human subjects, published in English, and investigating trazodone exposure during pregnancy. Keywords included \"pregnan*,\" \"trazodone,\" \"malformation*,\" and \"birth outcomes.\" Four reviewers independently extracted data from the selected records. Risk of bias was assessed using the Newcastle-Ottawa Scale. Data synthesis involved a qualitative analysis to summarize and interpret the findings, identifying patterns across the studies.</p><p><strong>Results: </strong>Fourteen studies met the inclusion criteria. The main outcome measures included fetal and pregnancy outcomes such as congenital malformations, developmental outcomes, poor neonatal adaptation syndrome (PNAS), persistent pulmonary hypertension of the newborn (PPHN), congenital heart defects, gestational age, birth weight, stillbirth, preterm birth, spontaneous and therapeutic abortion, and pre-eclampsia.</p><p><strong>Conclusion: </strong>The review found no consistent evidence linking trazodone use during pregnancy to increased risks of congenital malformations, stillbirths, or low birth weight. However, some studies suggested a possible association with an increased risk of spontaneous and therapeutic abortions. Given the limited and varied data, further research with larger, well-controlled studies are needed to establish the safety profile of trazodone during pregnancy. Overall, clarifying the specific risks and benefits of trazodone use in pregnancy will better guide clinical decision-making and improve maternal-fetal health outcomes.</p><p><strong>Trial registration: </strong>PROSPERO number: CRD42024503611.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"1401-1408"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682171","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":"From adoption to impact: linking prescribing tools to clinical outcomes-authors' response.","authors":"Monia Donati, Carlotta Lunghi, Giulia Grillini, Marco Domenicali, Maria Lia Lunardelli, Veronica Pasini, Susy Milandri, Monica Mussoni, Fabio Pieraccini, Elisa Sangiorgi, Emanuel Raschi, Valentina Colonnello, Elisabetta Poluzzi","doi":"10.1007/s00228-025-03888-6","DOIUrl":"10.1007/s00228-025-03888-6","url":null,"abstract":"","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"1537-1538"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706836","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":"Tool use isn't enough-outcomes matter.","authors":"Muhammad Zahir Shah, Azka Mustaan","doi":"10.1007/s00228-025-03887-7","DOIUrl":"10.1007/s00228-025-03887-7","url":null,"abstract":"","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"1539-1540"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706837","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":"Barriers and solutions for the European prescribing exam: a qualitative world café study.","authors":"Erik M Donker, Joost D Piët, David J Brinkman, Milan C Richir, Paraskevi Papaioannidou, Robert Likic, Emilio J Sanz, Thierry Christiaens, João N Costa, Fabrizio De Ponti, Milo Gatti, Ylva Böttiger, Cornelis Kramers, Michiel A van Agtmael, Jelle Tichelaar","doi":"10.1007/s00228-025-03886-8","DOIUrl":"10.1007/s00228-025-03886-8","url":null,"abstract":"<p><strong>Purpose: </strong>To harmonize and modernize clinical pharmacology and therapeutics (CPT) education across Europe, we developed the European Prescribing Exam. Before its introduction into medical degree programs, it is crucial to understand the potential barriers to its implementation and ways to overcome them. Therefore, the aim of this study was to identify barriers and potential solutions to the implementation of the European Prescribing Exam.</p><p><strong>Methods: </strong>This qualitative World Café (WC) study involved CPT teachers who participated in a 2-day event focused on the European Prescribing Exam. There were five tables in the WC, each dedicated to a different topic of implementation: (1) organization, (2) technical aspects, (3) content, (4) rollout logistics, and (5) politics. Participants rotated randomly between the tables every 20 min. During each round, they were encouraged to identify barriers and solutions, which were then discussed. The rounds continued until data saturation was reached. Findings were summarized at the end of the WC. We used inductive thematic analysis using a semantic approach to analyze the data.</p><p><strong>Results: </strong>In total, 26 CPT teachers (female: n = 14) from 19 medical schools in 15 European countries participated. After four rounds, 86 potential barriers and 86 solutions were identified. Most barriers were related to the topics \"Content\" (n = 22), \"Organization\" (n = 20), and \"Technical aspects\" (n = 18). Thematic analysis identified 11 themes, three of which were overarching, meaning they applied to multiple topics. The most significant themes included barriers related to curricula, motivation, information technology, and relevance.</p><p><strong>Conclusion: </strong>This study shows that organizing and implementing the European Prescribing Exam will be challenging. However, participants proposed potential solutions for nearly all barriers, which suggest that the implementation of the European Prescribing Exam is feasible.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"1451-1459"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12443867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717747","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}