Expert opinion on drug metabolism & toxicology最新文献

Esketamine for major depressive disorder: pharmacokinetics and toxicological considerations. 艾氯胺酮治疗重度抑郁症：药代动力学和毒理学考虑。

IF 3.4

Expert opinion on drug metabolism & toxicology Pub Date : 2026-05-06 DOI: 10.1080/17425255.2026.2671066

Shreya Vasudeva, Gabrielle Lovell, Joshua D Rosenblat

引用次数: 0

Exploring the influence of sex on idiosyncratic DILI: impact on prediction. 探讨性别对特异DILI的影响：对预测的影响。

IF 3.4

Expert opinion on drug metabolism & toxicology Pub Date : 2026-05-06 DOI: 10.1080/17425255.2026.2671065

Einar S Björnsson, Ayako Suzuki

{"title":"Exploring the influence of sex on idiosyncratic DILI: impact on prediction.","authors":"Einar S Björnsson, Ayako Suzuki","doi":"10.1080/17425255.2026.2671065","DOIUrl":"https://doi.org/10.1080/17425255.2026.2671065","url":null,"abstract":"Introduction: Idiosyncratic drug-induced liver injury (DILI) is a poorly understood condition which can be caused by various medications, including herbals and anti-cancer drugs. A literature review of studies published 1995-2025 was by search of PubMed and Google Scholar. Sex seems to play a role in the etiology of specific medication as women are more prone to DILI due to certain drugs, whereas male sex is a risk of factor of DILI due to other drugs.Areas covered: The current article highlight new studies on sex regarding risk factors of DILI, prediction of liver injury and predictors of severe outcomes. Studies on sex related differences in pharmacokinetics, and drug-specific differences of DILI are discussed. In addition the differences in the incidence of DILI and severity in women are discussed.Expert opinion: Although sex related differences have been reported, the reason for drug-specific risk factors for DILI are poorly characterized. A better understanding of drug vs. host related factors in terms of sex, is needed in order to predict the risk in women vs. men. Further studies need to determine if differences in different phenotypes and severity in women compared to men, are due to hormonal and/or pharmacokinetics or other factors.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147847685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

New insights into the role of CYP26 in retinoic acid clearance. CYP26在维甲酸清除中的作用的新见解。

IF 3.4

Expert opinion on drug metabolism & toxicology Pub Date : 2026-04-28 DOI: 10.1080/17425255.2026.2664480

Jamie Innes, Andrew Whiting, Peter McCaffery

{"title":"New insights into the role of CYP26 in retinoic acid clearance.","authors":"Jamie Innes, Andrew Whiting, Peter McCaffery","doi":"10.1080/17425255.2026.2664480","DOIUrl":"10.1080/17425255.2026.2664480","url":null,"abstract":"Introduction: All‑trans‑retinoic acid orchestrates vertebrate development and adult tissue homeostasis. Because both deficiency and excess are deleterious, atRA concentrations must be precisely controlled, making its local clearance essential. The cytochrome P450 family members CYP26A1/B1/C1 are the principal high‑affinity retinoic acid hydroxylases that terminate signaling and sculpt RA concentration gradients necessary for physiological homeostasis. Their inducibility by RA creates negative feedback whereby increased RA enhances its own clearance, shaping RA pharmacokinetics.Areas covered: Based on manual literature searching, this review integrates advances in CYP26 genetics, tissue expression, enzymology, and intracellular RA partitioning, and evaluates evidence linking CYP26 regulation to epithelial barrier biology, hepatic retinoid metabolism and disease, cancer stemness, musculoskeletal inflammation, and central nervous system retinoid homeostasis. Inhibitor discovery developments, including isoform-selective CYP26 inhibitors, are discussed, alongside therapeutic opportunities in dermatology, oncology, osteoarthritis, and CNS disorders.Expert opinion: CYP26 enzymes are underexploited therapeutic targets and gatekeepers of RA homeostasis. Promising avenues include topical and CYP26B1-preferential inhibition for keratinization disorders, exposure‑controlled combinations of atRA with RA-metabolism‑blocking agents in oncology and strategies that elevate endogenous RA signaling in inflammatory diseases. Progress will depend on biomarkers of RA exposure, improved isoform, and tissue selectivity, and trial designs that incorporate RA auto‑induction and metabolic variability.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"1-16"},"PeriodicalIF":3.4,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147793042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Microbiome-driven PKs: addressing research gaps and shaping future directions beyond the narrative review. 微生物组驱动的PKs：解决研究空白和塑造未来的方向超越叙事回顾。

IF 3.4

Expert opinion on drug metabolism & toxicology Pub Date : 2026-04-01 Epub Date: 2026-03-27 DOI: 10.1080/17425255.2026.2650187

Andrej Belančić, Almir Fajkić, Yun Wah Lam, Lejla Alić, Marc Labriffe, Kristina Pilipović, Amina Džidić-Krivić, Hing Yee Sy, Slobodan Jankovic

引用次数: 0

Pregnancy and epilepsy: pharmacokinetic insights into antiseizure medications. 妊娠和癫痫：抗癫痫药物的药代动力学见解。

IF 3.4

Expert opinion on drug metabolism & toxicology Pub Date : 2026-04-01 Epub Date: 2026-03-31 DOI: 10.1080/17425255.2026.2650186

Giovanni Falcicchio, Bruna Nucera, Loretta Giuliano, Giovanni Castellucci, Isabella Colonna, Emilio Russo

{"title":"Pregnancy and epilepsy: pharmacokinetic insights into antiseizure medications.","authors":"Giovanni Falcicchio, Bruna Nucera, Loretta Giuliano, Giovanni Castellucci, Isabella Colonna, Emilio Russo","doi":"10.1080/17425255.2026.2650186","DOIUrl":"10.1080/17425255.2026.2650186","url":null,"abstract":"Introduction: Absorption, distribution, metabolism and excretion of antiseizure medications may undergo significant modifications throughout pregnancy. These necessitate careful and proactive monitoring to avoid breakthrough seizures during pregnancy with potentially lethal consequences for both mother and child.Areas covered: Based on the available literature, pharmacokinetics of both older and newer antiseizure medications are examined by the authors, emphasizing the important available data and the missing ones for which it is necessary to expand knowledge.Expert opinion: Therapeutic drug monitoring is a valuable tool for tailoring antiseizure treatment in women with epilepsy. When monitoring is not feasible, clinicians may need to adjust doses based on seizure severity and the well-documented pharmacokinetic changes of specific medications such as lamotrigine, levetiracetam, oxcarbazepine. The goal is to maintain effective seizure control while minimizing teratogenic risks and ensuring safe fetal development.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"251-265"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147494689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An update on the pharmacokinetic and pharmacodynamic interactions between antidepressants and antiseizure medications. 抗抑郁药和抗癫痫药之间药代动力学和药效学相互作用的最新进展。

IF 3.4

Expert opinion on drug metabolism & toxicology Pub Date : 2026-04-01 Epub Date: 2026-03-25 DOI: 10.1080/17425255.2026.2650188

Edoardo Spina, Maria Antonietta Barbieri, Marika Alborghetti, Ferdinando Nicoletti, Jose de Leon

{"title":"An update on the pharmacokinetic and pharmacodynamic interactions between antidepressants and antiseizure medications.","authors":"Edoardo Spina, Maria Antonietta Barbieri, Marika Alborghetti, Ferdinando Nicoletti, Jose de Leon","doi":"10.1080/17425255.2026.2650188","DOIUrl":"10.1080/17425255.2026.2650188","url":null,"abstract":"Introduction: This is an update of a prior review of clinically relevant pharmacokinetic (PK) and pharmacodynamic (PD) drug-drug interactions (DDIs) between antidepressants and antiseizure medications (ASMs).Area covered: Articles published between 1 January 2010 and 30 November 2025 were identified through structured searches in PubMedⓇ, Web of Science, SCOPUS, and Google Scholar using antidepressant- and ASM-related terms. Some antidepressants, including fluoxetine, paroxetine, fluvoxamine, are moderate to strong inhibitors of various cytochrome P450 (CYP) isoenzymes and may cause clinically relevant interactions with ASMs metabolized by these pathways. First-generation ASMs with enzyme-inducing properties (e.g. carbamazepine, phenobarbital, and phenytoin) or enzyme-inhibiting effects (e.g. valproic acid) may alter the PK profile of several antidepressants, potentially leading to reduced therapeutic efficacy or dose-dependent toxicity. The introduction of second- and third-generation ASMs has substantially improved the safety of combined pharmacotherapy. Potential PD DDIs between antidepressants and ASMs are less clearly defined and remain largely theoretical.Expert opinion: Antidepressants and ASMs are associated with a considerable risk of clinically significant DDIs. A thorough understanding of the underlying PK and PD mechanisms, combined with complementary strategies including therapeutic drug monitoring, consultation of interaction databases, and careful clinical monitoring, is essential to anticipate, prevent, and effectively manage adverse DDIs.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"267-287"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147505975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Post-marketing pharmacovigilance of tedizolid: emerging safety signals. 泰德唑胺上市后的药物警戒：新出现的安全信号。

IF 3.4

Expert opinion on drug metabolism & toxicology Pub Date : 2026-04-01 Epub Date: 2026-04-15 DOI: 10.1080/17425255.2026.2660710

Haiping Yao, Guoping Gan, Zhu Wang

{"title":"Post-marketing pharmacovigilance of tedizolid: emerging safety signals.","authors":"Haiping Yao, Guoping Gan, Zhu Wang","doi":"10.1080/17425255.2026.2660710","DOIUrl":"10.1080/17425255.2026.2660710","url":null,"abstract":"Background: Tedizolid (TED), an oxazolidinone antibiotic, has improved pharmacokinetics compared with linezolid, but its real-world safety profile remains incompletely defined. Post-marketing surveillance helps detect adverse drug reactions (ADRs) not fully captured in clinical trials.Research design and methods: This retrospective pharmacovigilance study analyzed adverse event (AE) reports listing TED as the primary suspect drug in the U.S. FDA Adverse Event Reporting System (July 2014 - June 2025). Demographics, clinical indications, and outcomes were summarized descriptively. Disproportionality analyses-reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker-were applied at the system-organ class (SOC) and preferred term (PT) levels, requiring simultaneous positivity.Results: Among 14,919,217 AE reports, 494 involved TED. Hematologic toxicities were consistently detected, aligning with known risks. PT-level analysis identified potential emerging safety signals, including hepatic cytolysis, gamma-glutamyltransferase increased, mental status changes, tooth discoloration, and melena. Median onset among evaluable cases (n = 386) was three days, with nearly one-third occurring as true same-day events (Day 0).Conclusions: Post-marketing data confirm TED's hematologic risks and reveal additional potential hepatic, neuropsychiatric, and gastrointestinal signals. These findings merit further evaluation and prospective studies to clarify clinical significance, establish causality, and optimize monitoring strategies.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"289-298"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147679734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Impact of green tea on pharmacokinetics in cardiovascular therapy: current insights. 绿茶对心血管治疗药代动力学的影响：目前的见解。

IF 3.4

Expert opinion on drug metabolism & toxicology Pub Date : 2026-04-01 Epub Date: 2026-04-07 DOI: 10.1080/17425255.2026.2654467

Shingen Misaka, José Pablo Werba

引用次数: 0

Predicting the potential for organic cation transporter 1-mediated drug-drug interactions with fenoterol by amitriptyline, fluoxetine, selegiline, metformin, and verapamil. 通过阿米替林、氟西汀、塞来吉兰、二甲双胍和维拉帕米预测有机阳离子转运体1介导的药物与非诺特罗相互作用的可能性。

IF 3.4

Expert opinion on drug metabolism & toxicology Pub Date : 2026-03-19 DOI: 10.1080/17425255.2026.2643444

Alex Williams, Sorcha Mackle, Gabriele Sakinyte, Lorna Sholl, Nicole O'Shea, Charlotte Adshead, Robert Elsby

{"title":"Predicting the potential for organic cation transporter 1-mediated drug-drug interactions with fenoterol by amitriptyline, fluoxetine, selegiline, metformin, and verapamil.","authors":"Alex Williams, Sorcha Mackle, Gabriele Sakinyte, Lorna Sholl, Nicole O'Shea, Charlotte Adshead, Robert Elsby","doi":"10.1080/17425255.2026.2643444","DOIUrl":"https://doi.org/10.1080/17425255.2026.2643444","url":null,"abstract":"Background: Despite pharmacogenetic studies with human organic cation transporter (OCT) 1-deficient subjects presenting increased systemic concentrations of OCT1 substrates, highlighting clinical concern for potential drug-drug interactions (DDIs), specifically with the narrow therapeutic index substrate fenoterol, evaluation of new drug entities against OCT1 is not mandated by ICH M12.Research design and methods: Linear uptake (1 min, 0.831 µM = KM) of fenoterol was validated in HEK-293 cells overexpressing OCT1 as a prelude to assessing likely comedications (amitriptyline 0.03-30 µM, fluoxetine 0.1-100 µM, selegiline 1-1000 µM, metformin 300-300,000 µM, verapamil 0.06-60 µM) as inhibitors of OCT1. Ki values were integrated into mechanistic static equations to quantify potential DDI with object fenoterol.Results: Determined Ki values of 0.527 ± 0.276 µM, 5.08 ± 0.907 µM, 13.1 ± 5.73 µM, 7230 ± 1460 µM, and 0.339 ± 0.0994 µM for amitriptyline, fluoxetine, selegiline, metformin, and verapamil, predicted fenoterol AUCRs of 1.09, 1.06, 1.02, 1.02, and 2.11 due to hepatic OCT1 inhibition, respectively.Conclusions: An in vitro OCT1 inhibition assay using fenoterol as probe substrate was validated and identified that verapamil may pose a clinically relevant interaction risk, predicting a minimum 2-fold increase in fenoterol exposure. This highlights the need for caution when coadministrating verapamil with fenoterol and supports incorporating OCT1 inhibition profiling into preclinical evaluation of new drug entities to better inform clinical development and ensure patient safety.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"1-13"},"PeriodicalIF":3.4,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147489069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ADME investigations of novel therapeutic modalities: challenges and opportunities 2025. 新型治疗方式的ADME研究：挑战和机遇2025。

IF 3.4

Expert opinion on drug metabolism & toxicology Pub Date : 2026-03-01 Epub Date: 2026-03-30 DOI: 10.1080/17425255.2026.2650189

Hongbin Yu, Richard Dambra, Gary Chan, Elise Ishida, Ali Khalilimeybodi, Nicholas Krebs, Minu Ravindra Pilvankar, Swen Seeland

{"title":"ADME investigations of novel therapeutic modalities: challenges and opportunities 2025.","authors":"Hongbin Yu, Richard Dambra, Gary Chan, Elise Ishida, Ali Khalilimeybodi, Nicholas Krebs, Minu Ravindra Pilvankar, Swen Seeland","doi":"10.1080/17425255.2026.2650189","DOIUrl":"10.1080/17425255.2026.2650189","url":null,"abstract":"Introduction: Advancements in absorption, distribution, metabolism, and excretion (ADME) science and pharmacokinetics (PK) have reshaped the drug development landscape, markedly reducing clinical attrition due to unfavorable PK properties. As biotherapeutics become increasingly complex, dose optimization has emerged as a critical focus area to address remaining translation challenges, requiring comprehensive understanding and predictability of a drug candidate's PK and its relationships with pharmacodynamic (PD) effects.Areas covered: Emerging biotherapeutic modalities such as antibody-drug conjugates (ADCs), blood-brain barrier-penetrating bispecific antibodies, adeno-associated virus (AAV) gene therapy, and oncolytic viruses (OVs) present unique challenges for ADME and PK investigations given their complex composition and the dynamic biological processes governing their disposition. This review explores the distinctive ADME characteristics of these four modalities, highlighting challenges they pose to traditional PK paradigms and innovative strategies being developed to enhance preclinical-to-clinical translation. Literature search for this review was performed via PubMed database search between 30 September 2025 and 6 February 2026.Expert opinion: By integrating recent preclinical and clinical insights with advances in bioanalytical methods and mechanistic modeling, we present forward-looking perspectives on enabling more precise and effective dosing strategies for these complex modalities.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"181-199"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147501293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0