Fundamental & Clinical Pharmacology最新文献

{"title":"Variability in Sertraline Pharmacokinetics in Routine Clinical Practice: Influence of Sex, Age, Body Weight, Smoking, and Co-Medication","authors":"Begoña Tapia-Alzuguren,&nbsp;Covadonga Canga-Espina,&nbsp;Patricio Molero,&nbsp;Azucena Aldaz","doi":"10.1111/fcp.70114","DOIUrl":"10.1111/fcp.70114","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To investigate the influence of sex, age, body weight, smoking habits, and co-medications on sertraline pharmacokinetics in a routine clinical setting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective observational study analyzed 177 predominantly inpatient therapeutic drug monitoring records from 101 patients receiving sertraline as monotherapy or polytherapy. Pharmacokinetic parameters—serum concentrations (CSER), concentration-to-dose ratio (CDR), weight-normalized CDR (CDR/kg), apparent clearance (CL/F), and metabolite-to-parent ratio (N-SER/SER)—were compared across subgroups defined by sex, age (&lt; 18; 18–65; &gt; 65 years), BMI, smoking, and co-medications. To address the nonindependence of repeated measurements, analyses were complemented using linear mixed-effects models and a sensitivity analysis restricted to one observation per patient.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Descriptive analyses suggested higher CDR/kg in males and higher CSER in elderly patients. After accounting for within-patient clustering, the increase in CDR/kg across BMI categories remained the most consistent finding, likely reflecting mathematical normalization. The higher CSER observed in elderly patients persisted in the mixed-effects model but not in the sensitivity analysis, although the direction of effect remained consistent. Sex-related differences were not robust after adjustment and were largely attributable to body weight. Smoking showed no measurable effect. Among co-medications, carbamazepine showed the most consistent pharmacokinetic signal, whereas other findings were less consistent.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Elderly age may contribute to higher sertraline concentrations; however, its effect appears modest after accounting for clustering. Sex differences are largely explained by body weight, and smoking does not appear to influence pharmacokinetics. Carbamazepine showed a consistent induction pattern, whereas other co-medication findings should be considered exploratory.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 6","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/fcp.70114","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “The Hill-Langmuir Equation Governs Drug-Target Binding Kinetics for Pulsed Drug Delivery”","authors":"","doi":"10.1111/fcp.70115","DOIUrl":"https://doi.org/10.1111/fcp.70115","url":null,"abstract":"<p>\u0000 <span>Shi, X</span>, <span>The Hill-Langmuir Equation Governs Drug-Target Binding Kinetics for Pulsed Drug Delivery</span>. <i>Fundamental &amp; Clinical, Pharmacology</i>, <span>2026</span>: <span>40</span>:e700069\u0000 </p><p>In paragraph 2 of the Introduction section, the sentence:</p><p>should read:</p><p>This has been corrected in the online version of the article.</p><p>We apologize for this error.</p>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 6","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/fcp.70115","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149099969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin D Supplementation and Mortality in the Elderly: A Review of a Meta-Analysis of Randomized Controlled Trials Using the REB Method","authors":"Natalia Kostakis,&nbsp;Jean-Christophe Lega,&nbsp;Remy Boussageon","doi":"10.1111/fcp.70112","DOIUrl":"https://doi.org/10.1111/fcp.70112","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The results of randomized controlled trials (RCTs) regarding the effect of vitamin D supplementation on mortality reduction are conflicting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The aim of this study was to assess the level of evidence through a sensitivity analysis of the meta-analysis by Shah et al. (2024) using the Rebuilt the Evidence Base (REB) method.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The main inclusion criterion was a double-blind, placebo-controlled RCT design. The exclusion criteria were trials combining vitamin D with other nutrients and unpublished RCTs. The main outcome was all-cause mortality. A bias analysis was performed, followed by a hypothetico-deductive analysis to determine the confirmatory or exploratory nature of each RCT. The REB method was used to interpret the results and assess the level of evidence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the 25 RCTs included in the meta-analysis by Shah et al., the analysis was performed on 8 RCTs at low risk of bias including 30 320 participants. Seven RCTs raised some concerns, and two RCTs were at high risk of bias according to ROB2. Bias arose from the randomization process, deviations from intended interventions, missing outcome data, and selection of the reported results. The results were statistically significant, in favor of vitamin D supplementation: RR = 0.96 (95% CI [0.92, 1.00]), <i>p</i> = 0.04. No RCT was conclusive.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>According to the REB method, there is an evidence signal regarding the benefit of vitamin D supplementation in the population aged 75 and older, which remains to be confirmed.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 6","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/fcp.70112","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149099391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug News and Therapeutic News","authors":"","doi":"10.1111/fcp.70097","DOIUrl":"https://doi.org/10.1111/fcp.70097","url":null,"abstract":"","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 S1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149048229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Posters","authors":"","doi":"10.1111/fcp.70100","DOIUrl":"https://doi.org/10.1111/fcp.70100","url":null,"abstract":"","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 S1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149048231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discussed Posters","authors":"","doi":"10.1111/fcp.70099","DOIUrl":"https://doi.org/10.1111/fcp.70099","url":null,"abstract":"","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 S1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149047942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral Communication","authors":"","doi":"10.1111/fcp.70098","DOIUrl":"https://doi.org/10.1111/fcp.70098","url":null,"abstract":"","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 S1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149048230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Molecular Mechanisms of SB216763 in the Therapeutic Intervention of Pulmonary Fibrosis Based on Macrophage Functional Plasticity‌","authors":"Yunuo Zhou,&nbsp;Pei Zhou,&nbsp;Jianhong Qi","doi":"10.1111/fcp.70111","DOIUrl":"https://doi.org/10.1111/fcp.70111","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>SB216763 has demonstrated efficacy in treating pulmonary fibrosis in animal models, but its underlying mechanisms remain poorly understood. This study used network pharmacology, molecular docking, and molecular dynamics simulations to explore the molecular mechanisms by which SB216763 exerts therapeutic effects on pulmonary fibrosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The targets of SB216763 were screened using the PharmMapper database, while pulmonary fibrosis-related targets were obtained from GeneCards and OMIM databases. A Venn diagram generated from these datasets highlighted overlapping targets. Protein–protein interaction networks were constructed using the STRING database and Cytoscape software to assess target importance. GO and KEGG enrichment analyses using the Metascape database revealed relevant biological functions and signaling pathways of SB216763 in the treatment of pulmonary fibrosis. Molecular docking investigated the binding affinity and binding mode of SB216763 with GSK-3β. Molecular dynamics simulations further confirmed the stability of the complex formed by SB216763 and GSK-3β. Finally, Western blotting, Griess assays, and ELISA were employed to validate the effect of SB216763 on macrophage functional plasticity in pulmonary fibrosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Network pharmacology analysis identified the following three key targets of SB216763 in pulmonary fibrosis: AKT1, GSK3B, and TGFBR1, along with the PI3K-AKT signaling pathway. Molecular docking and dynamics simulations revealed that SB216763 primarily interacts with GSK-3β through hydrogen bonds and hydrophobic interactions. In vitro validation demonstrated significant anti-inflammatory and antifibrotic effects of SB216763. Additionally, SB216763 exhibited good safety in macrophages.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study provided new insights into the mechanisms of SB216763 in the treatment of pulmonary fibrosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Redefining Regulatory Proof: The End of the Two-Trial Paradigm","authors":"Jean-Christophe Lega,&nbsp;Steeve Provencher,&nbsp;Bruno Falissard,&nbsp;Clara Locher,&nbsp;Matthieu Roustit,&nbsp;Arthur Gougeon,&nbsp;Rémy Boussageon,&nbsp;Sylvie Chevret","doi":"10.1111/fcp.70110","DOIUrl":"https://doi.org/10.1111/fcp.70110","url":null,"abstract":"<p>The recent decision to establish a single pivotal trial as the default evidentiary standard for Food and Drug Administration (FDA) approval marks a substantive shift in the architecture of regulatory proof. This marks a shift from replication-based validation to a coherence-based model of sufficiency, beyond a procedural adjustment. Because FDA standards likely influence global development strategies, this change will likely extend beyond the United States. Although accelerating access and reducing development costs are legitimate objectives, the reform raises methodological and epistemological concerns. The statistical rationale does not fully incorporate the contextual factors that influence false-positive risk, including prior plausibility and statistical power. Prior plausibility remains informal, and post-marketing evidence seldom restores the epistemic security provided by independent replication. Replication is not merely a statistical redundancy but rather a structural safeguard of robustness and external validity. Without explicit safeguards, increased regulatory flexibility may generate heterogeneity in evidentiary thresholds and progressively weaken the discriminative function of health technology assessment.</p>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/fcp.70110","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148754007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"When Side Effects Become Therapies: A Mechanistic Taxonomy of Adverse Drug Reactions as Translational Signals for Drug Repositioning","authors":"Enzo Emanuele,&nbsp;Piercarlo Minoretti,&nbsp;Martina Ballerio,&nbsp;Alejandro Santos-Lozano,&nbsp;Simone Lista,&nbsp;Filippo Caraci,&nbsp;Robert Nisticò","doi":"10.1111/fcp.70109","DOIUrl":"10.1111/fcp.70109","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The systematic conversion of adverse drug reactions (ADRs) into new therapeutic indications represents one of the oldest and most productive sources of repositioned drugs; however, it has not been subjected to formal mechanistic analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This study aims to propose a mechanistic taxonomy of convertible ADRs and a structured workflow for translating documented adverse effects into testable repositioning hypotheses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this narrative review, historical cases of ADR-driven repositioning spanning five decades—from sildenafil and minoxidil to semaglutide—were analyzed and classified within a four-dimensional framework organized along the axes of: (1) target identity (on-target versus off-target conversion); (2) dose, route of administration, and reformulation; (3) patient population and clinical context; and (4) pharmacogenomic variability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Each historical case was successfully classified within the proposed taxonomy. A five-step theoretical workflow—comprising signal identification, taxonomic classification, mechanistic verification, feasibility assessment, and preliminary evidence search—was developed to operationalize the framework for prospective hypothesis generation. Computational tools including side-effect similarity networks, network pharmacology, and transcriptomic signature reversal were identified as means to support specific workflow steps.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The proposed taxonomy and workflow provide a replicable, mechanism-informed approach to ADR-driven drug repositioning, while also delineating the pharmacological, regulatory, and methodological challenges that separate a repositioning signal from an approved therapeutic indication.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148561841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}