British journal of clinical pharmacology最新文献

{"title":"Therapeutic reversal of cellular senescence: A systematic review of senolytics, senomorphics and anti-ageing therapies in human clinical trials.","authors":"Hitesha Trivedi, Suraj Tripathi, Jalay Thacker, Nilesh Patil, Sohel Shaikh","doi":"10.1002/bcp.70871","DOIUrl":"https://doi.org/10.1002/bcp.70871","url":null,"abstract":"<p><p>Cellular senescence, a key feature of ageing, involves irreversible cell cycle arrest and the secretion of pro-inflammatory senescence-associated secretory phenotype (SASP) factors, which contribute to tissue degeneration and age-related diseases. Targeting senescent cells with senolytics, senomorphics and anti-ageing therapies marks a major shift in translational geroscience, with the potential to delay or reverse age-related conditions. A systematic review and narrative synthesis was conducted in accordance with PRISMA 2020 guidelines. Eligible human clinical studies evaluating pharmacological interventions targeting cellular senescence were included, comprising randomized and nonrandomized clinical trials and pilot studies reporting clinical, functional or senescence-associated outcomes. Data on study characteristics, interventions, efficacy, safety and senescence-associated biomarkers were extracted and synthesized qualitatively. Six completed clinical studies were included in the evidence synthesis, with one additional ongoing clinical trial identified separately. Senolytic interventions, particularly dasatinib plus quercetin, showed preliminary improvements in selected functional outcomes and reductions in senescence-associated biomarkers, while senomorphic and mTOR-targeting interventions demonstrated effects on selected tissue and immune-related outcomes. Reported adverse events were generally mild or manageable, but small sample sizes and short follow-up limited assessment of uncommon and long-term safety risks. Current evidence suggests that pharmacological targeting of cellular senescence is feasible and may produce measurable biological and functional effects in humans, but evidence remains insufficient to establish clinical efficacy or long-term safety. Senolytic and senomorphic strategies should therefore be considered investigational rather than established therapies. Larger, adequately powered randomized trials with standardized senescence biomarkers, clinically meaningful outcomes, longer follow-up and systematic safety assessment are needed.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104338","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":"Beyond vulnerability: Is persistent opioid use in IBD a dynamic clinical phenotype?","authors":"Xiaopeng Chen, Amin Xie","doi":"10.1002/bcp.70868","DOIUrl":"https://doi.org/10.1002/bcp.70868","url":null,"abstract":"","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104272","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":"Prevalence of pregnancy and birth outcomes following biologic exposure in immune-mediated inflammatory diseases: A population-based study.","authors":"Leah K Flatman, Lisiane F Leal, Gabra Nohmie, Anick Bérard","doi":"10.1002/bcp.70848","DOIUrl":"https://doi.org/10.1002/bcp.70848","url":null,"abstract":"<p><strong>Aims: </strong>Almost 5% of pregnancies are affected by immune-mediated inflammatory diseases (IMIDs). As treatments become available, understanding their use during pregnancy is important. We aimed to describe maternal, pregnancy and infant outcomes among IMID pregnancies exposed to biologic therapies.</p><p><strong>Methods: </strong>Using the Merative™ MarketScan® Commercial Database, we identified pregnancies among mothers aged 15-45 with a pre-gestational IMID diagnosis. Biologic exposure during pregnancy was ascertained using prescription and procedure claims and classified by trimester. Outcomes included maternal complications, fetal/neonatal outcomes and pregnancy loss. Descriptive statistics were used to summarize characteristics, comorbidities, medication use and outcomes by biologic exposure status.</p><p><strong>Results: </strong>Among 257 409 IMID pregnancies, 6531 (2.5%) were exposed to biologics. Biologic-exposed pregnancies more frequently involved multiple IMIDs (34.9% vs. 7.7%). Nearly half of tumour necrosis factor inhibitor (TNFi) exposures occurred across all trimesters, while first-trimester-only exposure was more common for several non-TNFi biologics. Live births occurred in 77.4% of biologic-exposed pregnancies and 74.2% of biologic-unexposed pregnancies, with most births occurring at term. Maternal serious infections (i.e., infections requiring hospitalization) occurred in 19.7% of biologic-exposed pregnancies and 16.5% of unexposed pregnancies. Among 2066 biologic-exposed infants, the proportions of low birth weight and neonatal intensive care unit admission varied by specific non-TNFi biologics, whereas the distribution of neonatal outcomes appeared similar across exposure groups.</p><p><strong>Conclusion: </strong>Biologic use in IMID pregnancy increased over time and extended beyond the first trimester. Pregnancies with biologic exposure differed from unexposed pregnancies in disease characteristics and treatment patterns. Maternal and neonatal outcomes varied across biologic exposure groups.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104258","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 and pharmacokinetics of inhaled aloxistatin: A first-in-human phase 1 dose escalation trial.","authors":"Sebastian Fähndrich, Franziska Friedrich, Daniel Soriano, Jona Gjeloshi, Björn C Frye, Xuan Phuoc Nguyen, Lydia Herbstritt, Caroline von Spee-Mayer, Britta Lang, Fabrice Nollevaux, Andreas Hoheisel, Dorothee Winterberg, Armin Braun, Thomas Epting, Christine Contini, Karl Winkler, Thomas Reinheckel, Franziska C Trudzinski, Gernot Rohde, Daiana Stolz, Robert Bals, Martin J Hug, Sebastian Wirtz, Christoph Peters, Carolin Jenkner","doi":"10.1002/bcp.70858","DOIUrl":"https://doi.org/10.1002/bcp.70858","url":null,"abstract":"<p><strong>Aims: </strong>Aloxistatin (E64d) is a membrane-permeable cysteine protease inhibitor prodrug that is converted by esterases to the active metabolite E64c (loxistatin). This first-in-human study evaluated the safety, tolerability and pharmacokinetics of single ascending doses of inhaled E64d in healthy volunteers.</p><p><strong>Methods: </strong>In this randomized, double-blind, placebo-controlled phase 1 trial, 47 healthy male volunteers contributed 48 study participations across six dose cohorts. Thirty-six treatment assignments were to E64d and 12 to placebo. Study medication was administered by inhalation using a breath-triggered mesh nebulizer. Safety assessments included adverse events, pulmonary function, gas exchange, cardiovascular parameters, and laboratory variables. Plasma concentrations of E64d and E64c were characterized following inhalation.</p><p><strong>Results: </strong>No serious adverse events occurred, no adverse event was classified as severe and no participant discontinued because of an adverse event. Ten adverse events occurred following E64d and four following placebo; one mild event of mucosal dryness was considered treatment related. No clinically relevant changes were observed in pulmonary, cardiovascular, or laboratory safety assessments. E64d appeared rapidly and transiently in plasma, with a median T_max of 3 min. E64c showed sustained systemic exposure, with median T_max values of approximately 15-20 min and an elimination half-life of approximately 30-40 min across evaluable dose levels. Dose proportionality was not formally assessed.</p><p><strong>Conclusions: </strong>Single ascending doses of inhaled E64d were generally well tolerated in healthy male volunteers. Inhalation resulted in rapid, transient systemic exposure to E64d followed by measurable formation of E64c. These findings provide a safety and pharmacokinetic basis for further investigation of inhaled aloxistatin.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104228","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":"Lithium-related adverse drug reactions in children: A case-control study comparing lithium to second-generation antipsychotics in VigiBase.","authors":"Lisa T Ringeling, Ravish N Gangapersad, Lillian Lieuw, Patrick C Souverein, Eibert R Heerdink, Pilar Garcia-Gomez, Manon H J Hillegers, Birgit C P Koch, Bram Dierckx","doi":"10.1002/bcp.70827","DOIUrl":"https://doi.org/10.1002/bcp.70827","url":null,"abstract":"<p><strong>Aims: </strong>This study aimed to improve the understanding of lithium's safety profile by analysing the frequency and distribution of reported adverse drug reactions (ADRs) compared to second-generation antipsychotics (SGAs).</p><p><strong>Methods: </strong>Individual case safety reports from VigiBase (1968-October 2023) involving individuals older than 2 years, with lithium or SGAs as a suspected or interacting drug, were included. Medical Dictionary for Regulatory Activities (MedDRA) was used for ADRs classification. Proportional reporting ratios (PRRs) with 95% confidence intervals were calculated across different age groups.</p><p><strong>Results: </strong>The lithium group contained 29 897 reported ADRs. Proportional reporting patterns varied across age groups. In children, lithium was associated with a higher proportion of renal, endocrine, gastrointestinal, skin and cardiac ADRs compared to SGAs. SGAs showed proportionally more ADRs in females, whereas lithium displayed fewer and more balanced sex-related differences. Renal impairment accounted for a larger proportion of lithium-related ADRs in older adults compared to children. For SGAs, type 2 diabetes and cardiovascular events showed higher proportional reporting in both younger and older adults than in children. In contrast, thyroid-related ADRs with lithium and weight-related ADRs with SGAs were proportionally more common in children.</p><p><strong>Conclusions: </strong>Renal, endocrine and gastrointestinal effects are observed in children using lithium, though serious outcomes like renal failure appear proportionally more often in older adults. SGAs also show age-specific risk patterns, particularly metabolic and cardiovascular effects in adults. This emphasizes the ongoing need for individualized treatment and continued ADR monitoring and reporting to enhance the understanding of lithium's safety profile and support informed clinical decision-making.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104284","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":"Physiologically based pharmacokinetic modelling and dose optimization of tedizolid in paediatric patients.","authors":"Xueyong Li, Yu Cheng, Rongqi Lin, Jingping Shao, Luqi Lou, Tian Lin, Xuemei Wu, Hongqing Qiu","doi":"10.1002/bcp.70845","DOIUrl":"https://doi.org/10.1002/bcp.70845","url":null,"abstract":"<p><strong>Aims: </strong>Tedizolid is a next-generation oxazolidinone antibiotic approved for the treatment of acute bacterial skin and skin structure infections (ABSSSIs). This study aimed to develop a physiologically based pharmacokinetic (PBPK) model for tedizolid in adults and paediatric population.</p><p><strong>Methods: </strong>An adult PBPK model was built using GastroPlus®, incorporating physicochemical and pharmacokinetic parameters from the literature. The model was verified against clinical PK data from healthy adults and patients. It was then scaled to paediatric patients aged 2-18 years using age-dependent physiological changes. Paediatric model performance was validated against independent clinical data. Dose simulations evaluated once-daily intravenous and oral regimens targeting a free-drug area under the plasma concentration-time curve (AUC)/minimum inhibitory concentration (MIC) ratio (fAUC/MIC) of ≥3, with ≥90% probability of target attainment (PTA) across MIC values of 0.125-16 mg/L in immunocompetent patients.</p><p><strong>Results: </strong>The adult and paediatric PBPK models showed good predictive performance, with all predicted AUC and C_max values within the acceptable twofold error range and most observed concentrations falling within the 90% prediction interval. For children aged 2 to <12 years, intravenous and oral doses of ≥4 mg/kg achieved ≥90% PTA at an MIC of 0.5 mg/L. For adolescents aged 12 to <18 years, either a fixed 200 mg dose or a 3 mg/kg dose (intravenous or oral) achieved ≥90% PTA at an MIC of 0.5 mg/L.</p><p><strong>Conclusions: </strong>The paediatric PBPK model was successfully developed and identified model-derived candidate regimens for immunocompetent paediatric patients with ABSSSIs. These findings support further clinical evaluation of PBPK-guided dose optimization in children.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104218","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":"Relationship between continuous infusion meropenem PK/PD target attainment and C-reactive protein dynamics in onco-haematologic patients with febrile neutropenia.","authors":"Chun Liu, Pier Giorgio Cojutti, J G Coen van Hasselt, Michele Bartoletti, Maddalena Giannella, Pierluigi Zinzani, Pierluigi Viale, Federico Pea","doi":"10.1002/bcp.70667","DOIUrl":"10.1002/bcp.70667","url":null,"abstract":"<p><strong>Aim: </strong>Meropenem is a second-line antimicrobial agent in the treatment of febrile neutropenia in onco-haematological patients. A population pharmacokinetic/pharmacodynamic (PK/PD) analysis for assessing the relationship between meropenem exposure and C-reactive protein (C-RP) over time was conducted.</p><p><strong>Methods: </strong>Non-linear mixed-effect modelling was used to fit meropenem and C-RP concentrations. Monte Carlo simulations were conducted to assess median percentage reduction of C-RP from baseline associated with continuous infusion meropenem dosing, ensuring optimal PK/PD target attainment against Pseudomonas aeruginosa and Enterobacterales, namely, 100%t_{>4 × MIC}. Clinical outcome was assessed at the end of antimicrobial treatment.</p><p><strong>Results: </strong>A total of 141 patients were included in the analysis. A one-compartment model with estimated glomerular filtration rate as a covariate on drug clearance well-described meropenem pharmacokinetics. An indirect turnover maximum inhibition model was used to capture C-RP dynamics. Patients with C-RP Day 4/baseline ratio of <0.4 (fast response), between 0.4 and 0.8 (slow response) and >0.8 (no response) were 8.5%, 15.6% and 75.9%, respectively. Regression analysis showed that patients with fast and slow response patterns were associated with favourable clinical outcomes. Simulations showed that rapid and slow pattern patients reached C-RP reduction >90% from baseline at Days 6 and 10, respectively. No response pattern had C-RP peaking at Day 3 and eventually gradually reducing within 2 weeks.</p><p><strong>Conclusion: </strong>Despite optimal meropenem PK/PD target attainment, C-RP decreases in no more than one-fourth of onco-haematological patients during the first 2 weeks of treatment. Among no-response patients, C-RP should be associated with other biomarkers to discriminate subjects with favourable clinical outcome.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":"3646-3655"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13619083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374650","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":"Lowering salivary pH with sugar-containing gum augments salivary nitrite production and blood pressure reduction with dietary nitrate (beetroot juice).","authors":"Andrew J Webb, Harriet Clift, Callum Hill, Nur Mousa, Navanithan Arun Jayaraj, Jasmine Quraishi, Charlotte E Mills, Kevin O'Gallagher","doi":"10.1002/bcp.70640","DOIUrl":"10.1002/bcp.70640","url":null,"abstract":"<p><strong>Aims: </strong>The nitrate-nitrite-nitric oxide (NO) pathway has a wide range of effects including blood pressure (BP) regulation. Nitrate, produced endogenously, and absorbed from dietary sources (e.g., beetroot), is concentrated in/secreted by the salivary glands and reduced by lingual bacterial nitrate reductases to nitrite (the 'enterosalivary circulation'). Following systemic absorption, nitrite is further reduced to vasodilating NO intravascularly. The role of salivary pH in nitrate reduction has mainly been studied in isolated oral installation studies, rather than systemic studies employing the enterosalivary circulation. Our aim was to determine the acute relationship between salivary pH, salivary nitrite production, plasma [nitrite] and the BP-lowering effect of dietary nitrate, by altering salivary pH using sugar-containing chewing gum (vs. sugar-free chewing gum).</p><p><strong>Methods: </strong>We performed a 7-h crossover study, with 14 healthy volunteers consuming beetroot juice (Beet-It®, 70-mL, ~400-mg nitrate) and randomized to initially chew either sugar-containing acidic chewing (bubble) gum or sugar-free non-acidic chewing gum, with the alternate gum on the second visit.</p><p><strong>Results: </strong>Sugar-containing gum decreased salivary pH by 1.4 ± 0.09 vs. sugar-free gum (p < .0001). While there was no significant effect on salivary nitrate secretion or plasma [nitrate], salivary nitrite production was increased by 45% (30.0 ± 11.0 μmol·h^-1; [p < .01]), with plasma [nitrite] increasing by 25% (222.2 ± 50.3 nmol·L^-1; [p = .0001]). Systolic and diastolic BP were decreased by 2.7 ± 0.5 and 1.9 ± 0.5 mmHg, respectively (both p < .0001).</p><p><strong>Conclusion: </strong>Acutely lowering salivary pH (with sugar-containing gum) augments salivary nitrite production, plasma [nitrite] and BP-lowering with dietary nitrate. This mechanism has potential to enhance other nitrate-nitrite-NO pathway effects, for example, exercise performance.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":"3485-3494"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13619067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148276025","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":"Evaluating effectiveness of risk minimization through healthcare professional surveys: A review of post-authorization studies, 2022-2024.","authors":"Kexin Zhu, William A Blumentals, Froilan G Celzo, G Caleb Alexander, Lingyun Zhou, Juhaeri Juhaeri, Corinne Jouquelet-Royer, Jian-Yu E","doi":"10.1002/bcp.70647","DOIUrl":"10.1002/bcp.70647","url":null,"abstract":"<p><strong>Aims: </strong>Risk minimization measures (RMMs) are key regulatory tools to ensure safe medicinal product use. Regulatory guidelines recommend pre-specifying the targets, or 'thresholds', for assessing RMM effectiveness. We aimed to review recent industry-sponsored post-authorization safety studies (PASS) that evaluated the effectiveness of RMMs, focusing on the use and justification of predefined thresholds.</p><p><strong>Methods: </strong>We searched the Heads of Medicines Agencies-European Medicines Agency Catalogue to identify PASS evaluating the effectiveness of RMM through knowledge-based surveys of healthcare professionals. A total of 17 eligible studies in 2022-2024 were included in the descriptive analysis.</p><p><strong>Results: </strong>All studies used cross-sectional designs, and 70.6% were Category 3 PASS. Only 29.4% evaluated RMM effectiveness within the guideline-recommended time frame (12-24 months) following the launch and regulatory implementation of RMMs. Nearly all studies (16 of 17, 94.1%) predefined effectiveness thresholds. Overall, thresholds ranged from 60% to 80%, with the majority (88.2%) being set at 80%. Thresholds for assessing awareness, knowledge, utilization and behaviours were set at 80%, 80%, 60%-80% and 75%-80%, respectively. However, only eight studies (47.1%) provided rationales for threshold determination. Among them, six studies justified thresholds based on success rates applied in comparable studies or regulatory guidance, while two relied on subjective criteria without specifying prior knowledge, experience or established scientific evidence.</p><p><strong>Conclusion: </strong>Our findings suggest that although most industry-sponsored PASS evaluating RMM effectiveness included predefined thresholds, these were often applied to the knowledge indicator rather than awareness, utilization and behaviour indicators. Notably, only about half of the studies provided clear justifications for threshold selection. Clear success threshold justifications are essential for interpreting RMM effectiveness.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":"3495-3502"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13619043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148270330","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":"Anti-seizure medications and DRESS in paediatric patients: A FAERS disproportionality and time-to-onset analysis.","authors":"Ting Yang, Chaoyang Chen, Xuanling Zhang, Lingyue Ma, Ying Zhou","doi":"10.1002/bcp.70677","DOIUrl":"10.1002/bcp.70677","url":null,"abstract":"<p><strong>Aims: </strong>Anti-seizure medications (ASMs) are in the list of the most common drug culprits of drug reaction with eosinophilia and systemic symptoms (DRESS). However, no study has systematically evaluated DRESS associated with ASMs in a large paediatric cohort. This study aimed to investigate association of DRESS with ASMs and to characterize the onset pattern of ASM-related DRESS in paediatrics using FDA Adverse Event Report System (FAERS) database.</p><p><strong>Methods: </strong>FAERS data from the first quarter of 2004 to the second quarter of 2025 were analysed using R software (version 4.5.1). For signal detection of ASM-related DRESS in paediatric patients, disproportionality analysis was performed with four methods, consisting of Reporting Odds Ratio, Proportional Reporting Ratio, Bayesian Confidence Propagation Neural Network and Multi-Item Gamma Poisson Shrinker. Cumulative incidence was estimated using Kaplan-Meier method, and time-to-onset (TTO) analysis was conducted with Weibull distribution test.</p><p><strong>Results: </strong>Nine hundred forty-one reports of ASMs-related DRESS in paediatric population from FAERS database were analysed. Positive signals for DRESS were identified for lamotrigine, carbamazepine, levetiracetam, phenytoin, valproic acid, oxcarbazepine, phenobarbital, zonisamide, clobazam, ethosuximide, perampanel, fosphenytoin and eslicarbazepine. Ninety-eight cases were included in the TTO analysis. Lamotrigine, carbamazepine, levetiracetam and zonisamide demonstrated a wear-out failure-type pattern. Phenytoin, valproic acid and oxcarbazepine presented a random failure-type profile.</p><p><strong>Conclusions: </strong>Significant signals of DRESS associated with 13 ASMs were identified in paediatric populations. Notably, signals were detected for the first time for ethosuximide, perampanel, fosphenytoin and eslicarbazepine by disproportionality analysis. TTO analysis demonstrated wear-out or random failure-type patterns in the occurrence of ASM-associated DRESS.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":"3676-3686"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374709","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}