European Journal of Clinical Pharmacology最新文献

{"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}

{"title":"Novel pharmaceutical treatment approaches for schizophrenia: a systematic literature review.","authors":"Anan Jarab, Walid Al-Qerem, Adam Khdour, Heba Awadallah, Yousef Mimi, Maher Khdour","doi":"10.1007/s00228-025-03809-7","DOIUrl":"10.1007/s00228-025-03809-7","url":null,"abstract":"<p><strong>Purpose: </strong>Schizophrenia is a chronic and debilitating neuropsychiatric disorder affecting approximately 1% of the global population. Traditional antipsychotic treatments, while effective for positive symptoms, often have significant side effects and fail to address cognitive and negative symptoms. Novel pharmacological treatments targeting muscarinic receptors, TAAR1 agonists, serotonergic pathways, and glutamate modulation have emerged as promising alternatives.</p><p><strong>Aim: </strong>This systematic literature review aims to critically evaluate the efficacy, safety, and mechanisms of action of novel pharmacological agents in the treatment of schizophrenia.</p><p><strong>Methods: </strong>A comprehensive search was conducted across PubMed, Embase, Cochrane Library, Scopus, and Web of Science for randomized controlled trials (RCTs) and clinical trials published between April 2014 and March 2024. Studies evaluating novel treatments targeting muscarinic receptors, TAAR1 agonists, serotonergic agents, and glutamate modulation were included. Primary outcomes focused on symptom reduction and quality of life, while secondary outcomes included cognitive function and adverse events. The Joanna Briggs Institute (JBI) tool was used for quality assessment.</p><p><strong>Results: </strong>Eleven studies involving 4614 participants (mean age 37-43 years, predominantly male) were included. Drugs evaluated included xanomeline-trospium (KarXT), pimavanserin, ulotaront, emraclidine, and bitopertin. Significant improvements in PANSS and CGI-S scores were observed, with xanomeline-trospium showing a mean reduction of 17.4 points (p < 0.001). Adverse events were mostly mild and transient, with nausea, constipation, and somnolence being common.</p><p><strong>Conclusion: </strong>Novel treatments for schizophrenia show promise in managing both positive and negative symptoms, with generally favorable safety profiles. Future studies should focus on large-scale, long-term trials to refine their efficacy, safety, and clinical applicability.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"525-541"},"PeriodicalIF":2.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413715","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 dapagliflozin on malignant ventricular arrhythmias in elderly after acute myocardial infarction: a propensity score-matched cohort study.","authors":"Li Deng, Jingyi Wang, Ye Deng, Jianya Huang, Qingqing Gu, Qianwen Chen, Lu Pan, Jun Wei, Qingjie Wang, Ling Sun","doi":"10.1007/s00228-025-03832-8","DOIUrl":"https://doi.org/10.1007/s00228-025-03832-8","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to evaluate the effect of dapagliflozin (DAPA) on malignant ventricular arrhythmias (MVA) after acute myocardial infarction (AMI).</p><p><strong>Methods: </strong>A single-center, prospective and observational cohort study was conducted. We enrolled AMI patients from the ChangZhou Acute Myocardial Infarction Registry between January 2018 and November 2023. They were divided into two groups according to the use of dapagliflozin. The median follow-up time was 211 days. The primary endpoint of the study was the incidence of MVA during hospitalization, and the secondary endpoint was all-cause mortality rate during the follow-up period. Kaplan-Meier survival analysis and multifactorial logistic regression analysis were performed to assess the association between DAPA and the risk of MVA. Enrolled patients were matched on a 1:1 propensity score.</p><p><strong>Results: </strong>Of the 2607 AMI patients enrolled, MVA were reported postoperatively in 123 (4.7%)patients. Cardiovascular death occurred in 93 (3.6%) patients. The average age of the enrolled patients was 65.03 ± 0.27 years. Of participants assigned to dapagliflozin, 8 out of 363 patients (2.2%) experienced MVA compared with 115 out of 2244 patients (5.1%) in the control group (odds ratio, OR = 0.392; 95% confidence interval, 95% CI: 0.171-0.900; P = 0.027). After 1:1 propensity score matching, DAPA remained able to reduce the risk of MVA in patients with AMI. (OR = 0.340; 95% CI: 0.121-0.960; P = 0.042). At a median follow-up of 211 days, all-cause mortality remained lower in the DAPA group than in the control group after matching (P = 0.033).</p><p><strong>Conclusion: </strong>Dapagliflozin may attenuate the risk of MVA and all-cause mortality in elderly AMI patients, highlighting its potential as a therapeutic adjunct. However, these findings require validation in large-scale randomized trials.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751775","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":"Safety profiles of fondaparinux in pregnant women: a systematic review and meta-analysis.","authors":"Dan Shan, Jinbiao Han, Yurou Ji, Yuexiao Wu, Ke Yi","doi":"10.1007/s00228-025-03804-y","DOIUrl":"10.1007/s00228-025-03804-y","url":null,"abstract":"<p><strong>Background: </strong>The prevalence of conditions necessitating anticoagulation therapy among pregnant women has been steadily increasing. Although low-molecular-weight heparin (LMWH) is commonly used, several studies have investigated the use of fondaparinux in pregnant women. However, the safety profile of fondaparinux in this population remains to be fully elucidated.</p><p><strong>Methods: </strong>A comprehensive literature search across ten databases was conducted in September 2024. This meta-analysis was conducted following the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines for systematic reviews of observational studies. Dichotomous data from eligible studies were combined using the Mantel‒Haenszel model. Standard mean differences with 95% confidence intervals were assessed. Heterogeneity was evaluated using I² statistics and the Cochran Q test, and the quality of evidence was appraised using Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach.</p><p><strong>Results: </strong>Nine studies met the inclusion criteria. Based on the GRADE approach, the quality of evidence ranged from very low to low. Fondaparinux did not increase the incidence of bleeding-related adverse events (vaginal bleeding: OR = 0.99, 95% CI 0.43-2.30, P = 0.98; postpartum haemorrhage: OR = 0.35, 95% CI 0.07-1.73, P = 0.20). Fondaparinux was associated with reduced risks of hepatic transaminase elevation (OR = 0.20, 95% CI 0.08-0.49, P < 0.01), gastrointestinal reactions, allergies, and injection site skin reactions (OR = 0.19, 95% CI 0.09-0.41, P < 0.01).</p><p><strong>Conclusion: </strong>The findings of this systematic review and meta-analysis suggest that the use of fondaparinux among pregnant women has certain advantages. However, these conclusions warrant further validation through high-quality, large-scale studies conducted in multiple countries. (PROSPERO-CRD42024591579).</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"465-477"},"PeriodicalIF":2.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002569","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":"Grade ≥ 3 hematologic adverse events of immunotherapy in advanced NSCLC patients: a systematic review and meta-analysis.","authors":"Shuang Wang, Mengting Cai, Yajun Xiong, Tianyi Guo, Xiaoya Niu, Yu Chen, Yuying Feng, Chunhua Song, Aiguo Xu","doi":"10.1007/s00228-025-03803-z","DOIUrl":"10.1007/s00228-025-03803-z","url":null,"abstract":"<p><strong>Background: </strong>The impact of incorporating immune checkpoint inhibitors (ICIs) into standard chemotherapy on the severity and risk of myelosuppression in advanced non-small cell lung cancer (NSCLC) patients remains uncertain.</p><p><strong>Methods: </strong>We conducted a systematic review and meta-analysis of phase 3 randomized controlled trials (RCTs) that evaluated ICIs in people with NSCLC. A comprehensive search of four databases, PubMed, Web of Science, Embase, and the Cochrane Library, was carried out from inception to 30 October 2023. Pooled analyses assessed the risk ratios (RR) for treatment-related hematological adverse events greater than or equal to grade 3. The protocol is registered with PROSPERO and has the CRD42024500056 registration number.</p><p><strong>Findings: </strong>Twenty-three phase 3 RCTs were contained, involving 15,844 people with NSCLC receiving ICIs with or without chemotherapy. Compared with chemotherapy alone, ICI monotherapy or dual immunotherapy reduced treatment-associated leukopenia (relative risk (RR) 0.03, 95% CI 0.01-0.08), neutropenia (RR 0.02, 95% CI 0.01-0.03), thrombocytopenia (RR 0.05, 95% CI 0.02-0.14), and anemia (RR 0.09, 95% CI 0.05-0.15), with a pooled incidence of 0.07%, 0.08%, 0.14%, and 9.07%. Compared with chemotherapy alone, ICIs in combination with chemotherapy increased the risk of developing treatment-related thrombocytopenia (RR 1.35, 95% CI 1.04-1.77), with a pooled incidence rate of 6.83%; it did not increase leukopenia (RR 0.97, 95% CI 0.70-1.35), neutropenia (RR 1.05, 95% CI 0.90-1.23), and anemia (RR 1.10, 95% CI 0.85-1.43), with pooled incidence rates of 4.47%, 14.67%, and 13.36%, respectively.</p><p><strong>Interpretation: </strong>For patients with advanced or metastatic NSCLC, severe hematological adverse events are uncommon when ICIs are used alone, as opposed to chemotherapy. However, when used in conjunction with chemotherapy, these side effects may be intensified, particularly in the form of an elevated incidence of thrombocytopenia of grade 3 or higher.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"479-493"},"PeriodicalIF":2.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002517","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":"Prognostic value of IMDC score in non-small cell lung cancer receiving immunotherapy: old dog, new tricks? : IMDC in lung cancer immunotherapy.","authors":"İsmail Beypınar, Semiha Urvay, Müslih Ürün, Berrak Erçek, Hacer Demir, Canan Yıldız, Murat Araz, Ahmet Oruç, Utku Özilice, Onur Yazdan Balçık","doi":"10.1007/s00228-025-03810-0","DOIUrl":"10.1007/s00228-025-03810-0","url":null,"abstract":"<p><strong>Background: </strong>Although there are multiple treatment options, oncologists lack appropriate biomarkers for determining the efficacy and toxicity of immunotherapy. In this study, we aimed to use a combination of the clinical parameters of IMDC risk groups at the time of diagnosis to predict the effectiveness of immunotherapy.</p><p><strong>Methods: </strong>This multicenter cross-sectional study retrospectively analyzed non-small cell lung cancer (NSCLC) patients receiving nivolumab for the prognostic effects of clinical factors, including the IMDC score.</p><p><strong>Results: </strong>Two hundred and five patients were enrolled in this study. There was no favorable group because the TTI was less than 1 year in the entire study group in the IMDC. The IMDC score and IMDC groups showed significant differences in PFS (p < 0.001; p < 0.001, respectively). Intermediate and poor-risk groups had PFS of 8 and 3 months PFS, respectively. The IMDC group showed a significant effect on OS (p = 0.002). The intermediate- and poor-risk groups had 12- and 4-month OS, respectively. The TTI risk factor excluded patient numbers in the favorable, intermediate, and poor risk groups were 47, 129, and 29, respectively, in the revised IMDC group (rIMDC). The prognostic effect of the rIMDC score and groups remained significant (p < 0.001 and p < 0.001, respectively). The classical IMDC had a significant effect on PFS in the multivariate analysis (p = 0.016). Also, rIMDC score in multivariate analysis resulted with significant effect on OS (p = 0.035).</p><p><strong>Conclusion: </strong>To date, this is the first study to prove that the IMDC may be a valuable option for predicting both prognosis and treatment efficacy in NSCLC patients receiving especially second or further lines nivolumab treatment.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"561-570"},"PeriodicalIF":2.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457347","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":"Evaluating the safety and efficacy of nirmatrelvir-ritonavir therapy in pregnant women with COVID-19: a systematic review and meta-analysis.","authors":"Omar Hassan, Aya Abdulkarim Elbhairy, Aya Magdy Siam, Tasneem Abdelwahab, Albraa Ashraf Hamad, Omar Ehab Mahmoud, Omnia Azmy Nabeh","doi":"10.1007/s00228-025-03808-8","DOIUrl":"10.1007/s00228-025-03808-8","url":null,"abstract":"<p><strong>Purpose: </strong>Pregnant women are at heightened risk for severe COVID-19 outcomes. However, treatment options during pregnancy remain limited due to concerns over their safety and efficacy.</p><p><strong>Methods: </strong>This systematic review and meta-analysis assessed the safety and efficacy of nirmatrelvir-ritonavir in pregnant women diagnosed with mild-to-moderate COVID-19. The analysis focused on cases where the treatment was initiated within five days of symptom onset. A single-arm meta-analysis was performed to comprehensively evaluate outcomes across maternal, delivery, and neonatal domains.</p><p><strong>Results: </strong>In line with PRISMA guidelines, six studies involving a total of 427 pregnant patients were included in the analysis. Hospitalization was reported in 2% of patients (95% CI: 1%-5%), with low heterogeneity across studies (I² = 21.9%). Drug discontinuation and new-onset gestational diabetes (NOGDM) had a pooled estimate of 0.7% (95% CI: 3% to 15%) and 4.0% (95% CI: 1% to 16%), respectively, with substantial heterogeneity (I² = 64.7% and 66.5%), respectively. New-onset gestational hypertension (NOGHTN) had a pooled estimate of 4% (95% CI: 1% to 26%), with considerable heterogeneity (I² = 78.81%). For neonatal outcomes, the pooled estimate for birth weight was 3186 g (95% CI: 3123-3248 g; I² = 0%), and no maternal or neonatal deaths were reported across the included studies.</p><p><strong>Conclusion: </strong>Nirmatrelvir-ritonavir appears safe and effective for mild-to-moderate COVID-19 in pregnant women, with low rates of hospitalization and adverse maternal outcomes. Larger, randomized studies are crucial to confirm these findings and ensure safety in diverse populations.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"495-506"},"PeriodicalIF":2.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413713","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":"Psychotropic polypharmacy impairs walking independence in post-stroke patients.","authors":"Ayaka Matsumoto, Yoshihiro Yoshimura, Fumihiko Nagano, Sayuri Shimazu, Takahiro Bise, Yoshifumi Kido, Ai Shiraishi, Aomi Kuzuhara, Takenori Hamada, Kouki Yoneda","doi":"10.1007/s00228-025-03833-7","DOIUrl":"https://doi.org/10.1007/s00228-025-03833-7","url":null,"abstract":"<p><strong>Purpose: </strong>Psychotropic drugs are associated with adverse outcomes in older adults. However, evidence on the effect of psychotropic use on walking ability in post-stroke patients is lacking. This study examined the association between psychotropic medication use and walking independence in post-stroke patients.</p><p><strong>Methods: </strong>This retrospective cohort study included stroke patients admitted for convalescent rehabilitation at a Japanese hospital between 2020 and 2022. Psychotropic medications (benzodiazepines, hypnotics, antipsychotics, and antidepressants) prescribed at admission were recorded. The primary outcome was walking independence at discharge, defined as a Functional Independence Measure (FIM) walk score ≥ 6. Logistic regression analyses examined the association between the number of psychotropic drugs and walking independence, adjusting for potential confounders.</p><p><strong>Results: </strong>Of the 709 patients enrolled, 559 (mean age 75.5 years, 52.8% male) were included in the analysis. At admission, 25.4% of patients used psychotropic drugs. In the adjusted analysis, the number of psychotropic medications was independently associated with lower walking independence at discharge (OR 0.620, 95% CI 0.428-0.897, P = 0.011). Hypnotic use specifically showed a negative impact on walking independence (OR 0.331, 95% CI 0.154-0.708, P = 0.004). However, psychotropic drug use was not significantly associated with improvement in FIM-motor scores.</p><p><strong>Conclusion: </strong>Psychotropic polypharmacy at admission, particularly with hypnotics, was associated with reduced likelihood of achieving walking independence after stroke rehabilitation. Judicious use of psychotropic medications may be warranted when ambulation is a critical goal for older post-stroke patients.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751780","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":"Reply to correspondence.","authors":"Omar Ismail, Karam Albdour, Yazan Jaber, Kamel Jaber, Ameen Alsaras","doi":"10.1007/s00228-025-03827-5","DOIUrl":"https://doi.org/10.1007/s00228-025-03827-5","url":null,"abstract":"","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709287","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":"Exploring the comprehensive factors influencing tacrolimus pharmacokinetics in early renal transplant recipients: A population pharmacokinetic analysis.","authors":"Yan Zhang, Ling Xue, Linkun Hu, Liangliang Wang, Hao Pan, Yuxin Lin, Xiaoliang Ding, Yuhua Huang, Liyan Miao","doi":"10.1007/s00228-025-03825-7","DOIUrl":"https://doi.org/10.1007/s00228-025-03825-7","url":null,"abstract":"<p><strong>Purpose: </strong>To establish a population pharmacokinetic (PopPK) model of tacrolimus in the early stages after renal transplantation and evaluate the model's predictive performance with external data.</p><p><strong>Methods: </strong>Intravenous and oral tacrolimus were administered to 302 renal transplant recipients in the early posttransplantation stages. Related data were obtained from the electronic medical records. Single nucleotide polymorphisms in genes associated with tacrolimus pharmacokinetics were tested. The data were analyzed by NONMEM. The external data from 153 patients were subsequently used to evaluate model extrapolation.</p><p><strong>Results: </strong>A one-compartment model was used to determine tacrolimus pharmacokinetics. The estimated clearance (CL), volume of distribution (V) and bioavailability (F) of tacrolimus were 4.91 L/h, 77 L and 26.5%, respectively. CL and V decreased with increasing hematocrit. CL and F decreased with increasing operation time. Diltiazem and Wuzhi capsule resulted in 28.4% and 43.9% decreases in the CL, respectively. Omeprazole or esomeprazole resulted in a 9% increase in F. The value of F for patients expressing CYP3A5 was 36.6% lower than that for the patients who did not express CYP3A5. The evaluation of external data revealed that the proportion of individual prediction error within 20% of the observed tacrolimus concentration was greater than 77.3%.</p><p><strong>Conclusions: </strong>A PopPK model for tacrolimus was established for early renal transplantation. CYP3A5 was a significant covariate for F. Fat-free mass was the best predictor of the influence of body size on CL and V. The model could be extrapolated to stable renal transplant recipients.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700040","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}