DRUG METABOLISM REVIEWS药物代谢评论
DRUG METABOLISM REVIEWS(英文缩写 DRUG METAB REV),ISSN 0360-2532,eISSN 1097-9883,中文译名:药物代谢评论 是一本学术期刊。本页汇总该期刊的最新影响因子、分区信息以及最新收录于 PubMed 的文献,帮助您快速了解期刊全貌。
发文量统计区间：2025-11-01 至 2026-10-31，按本站收录文献的发表日期统计。
期刊介绍
历年影响因子趋势
| JCR 数据年份 | 影响因子 | JCR 分区 |
|---|---|---|
| 2021 | 6.984 | Q1 |
| 2022 | 5.900 | Q1 |
| 2023 | 3.400 | Q2 |
| 2024 | 3.800 | Q2 |
| 2025 | 4.700 | Q1 |
DRUG METABOLISM REVIEWS 最新收录文献
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1. Reprogramming of hepatic drug metabolism following early-life xenobiotic exposure: insights from nuclear receptor pathways.
1. 生命早期外源物暴露后肝脏药物代谢的重编程：来自核受体通路的见解PMID:日期:2026-09-16Substantial interindividual variability in the expression and activity of drug-metabolizing enzymes (DMEs) contributes to variability in drug disposition and response. Early-life, encompassing the fetal and neonatal periods, is a critical developmental window for the establishment and functional programming of the hepatic DME system. Exposure to xenobiotics such as pharmaceuticals, environmental pollutants, inflammatory mediators, and nutritional interventions during this vulnerable period can exert long-term programming effects on hepatic drug metabolism. These effects are mediated primarily through the disruption of nuclear receptor signaling networks, ultimately altering hepatic drug-metabolizing capacity and potentially influencing susceptibility to altered drug responses in later life. This review systematically examines the pivotal roles of the constitutive androstane receptor, pregnane X receptor, and glucocorticoid receptor in mediating the reprogramming of DME expression following early-life xenobiotic exposure. Furthermore, it delineates how epigenetic reprogramming, with a particular focus on histone modifications, converts nuclear receptor-derived signals into persistent transcriptional memories, thereby consolidating the long-term phenotypic effects of early-life events. Additionally, the review integrates evidence on how endogenous factors, including inflammation and nutritional status, modulate drug metabolic programming by regulating nuclear receptor networks. Framed within the Developmental Origins of Health and Disease paradigm, this review elucidates the mechanistic foundations of interindividual differences in drug responses. The insights provided herein aim to provide a critical scientific basis for understanding the long-term consequences of early-life exposure and informing future research on risk assessment and translational evaluation.
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2. Metabolism-driven hepatotoxicity of 5-fluorouracil: molecular mechanisms and future therapeutic directions.
2. 5-氟尿嘧啶的代谢驱动肝毒性：分子机制和未来治疗方向PMID:日期:2026-09-025-Fluorouracil (5-FU) is a widely used chemotherapeutic agent for the treatment of various solid malignancies; however, its clinical application is also associated with hepatotoxicity. As the liver is the primary site of 5-FU metabolism, excessive accumulation of the drug and its metabolites can lead to hepatic injury through multiple interconnected mechanisms. This review summarizes the current understanding of the 5-FU metabolism and molecular pathways involved in 5-FU-induced liver damage. Evidence indicates that 5-FU induces oxidative stress,which is a key event in its hepatotoxicity, characterized by excessive generation of ROS, depletion of antioxidant defenses, and oxidative damage to cellular macromolecules. Increased oxidative stress promotes lipid peroxidation, DNA damage, and mitochondrial dysfunction, ultimately leading to hepatocyte death. 5-FU-induced apoptosis is mediated by the activation of p53 signaling, disruption of the Bcl-2-associated X protein (Bax)/B-cell lymphoma 2 (Bcl-2) balance, subsequent cytochrome c release, caspase activation, and DNA fragmentation. 5-FU induces Inflammatory responses by activation of nuclear factor kappa B signaling and transcription of pro-inflammatory cytokines, further aggravating hepatic injury. Emerging studies also suggest that necroptosis and activation of the NOD-like receptor pyrin domain-containing protein 3 inflammasome contribute to the progression of 5-FU-induced liver injury. Additionally, impairment of mitochondrial fatty acid β-oxidation contributes to lipid accumulation and hepatic steatosis. Despite significant advances in understanding the pathogenesis of 5-FU-induced hepatotoxicity, several molecular pathways remain insufficiently explored. A comprehensive understanding of these mechanisms may facilitate the development of effective hepatoprotective interventions and improve the safety of 5-FU-based chemotherapy.
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3. Metabolic pharmacology of anthelmintic drugs targeting mitochondrial fumarate reductase in neurocysticercosis.
3. 靶向线粒体富马酸还原酶的抗蠕虫药物在神经囊尾蚴病中的代谢药理学PMID:日期:2026-08-26Neurocysticercosis (NCC), caused by larvae in the central nervous system, is a significant cause of acquired epilepsy. The cysts' resistance to standard treatments highlights the need for new metabolic targets, particularly the anaerobic respiratory pathways in helminth mitochondria. Cestodes exhibit metabolic flexibility, utilizing the fumarate reductase (FRD) complex to thrive in low-oxygen environments, using rhodoquinone (RQ) for electron transfer. This unique system enables them to convert fumarate to succinate, essential for energy generation. The effectiveness of benzimidazole-based chemotherapy relies on factors like metabolism and tissue distribution, with the RQ-dependent system absent in humans, making it a selective chemotherapy target.Benzimidazoles like albendazole inhibit the FRD complex in parasites by binding to a unique quinone-binding pocket. This action halts the anaerobic electron transport chain, causing energy depletion and mitochondrial damage. The result is osmotic imbalance, tegumental rupture, and release of antigens that heighten the host immune response. Additionally, FRD inhibition leads to significant bioenergetic changes, including disrupted succinate levels, increased glycolysis, and a breakdown of mitochondrial adaptability, ultimately removing the metabolic safety net necessary for parasite survival in low-oxygen environments, which aids in host clearance of the parasite.This review critically examines the metabolic pharmacology of FRD-targeting anthelmintics, synthesizes current evidence on their mechanisms of action and metabolic consequences, and highlights emerging metabolomics-based opportunities for improving therapeutic strategies against neurocysticercosis.
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4. SAR and mechanistic pathways of oxadiazole derivatives: targeting enzymes for antidiabetic therapy.
4. 噁二唑衍生物的构效关系及机制途径：靶向酶用于抗糖尿病治疗PMID:日期:2026-08-24The global prevalence of diabetes mellitus continues to rise sharply, creating an urgent need for effective strategies to manage postprandial hyperglycemia. Inhibition of the carbohydrate-hydrolysing enzymes α-glucosidase and α-amylase is a well-established approach for reducing glucose absorption and improving glycaemic control. Among the heterocyclic scaffolds investigated for antidiabetic drug discovery, oxadiazoles have attracted particular attention because of their structural versatility, balanced electronic properties, and capacity to engage enzyme active sites through hydrogen bonding, π-π stacking, hydrophobic contacts, and van der Waals interactions. Several oxadiazole derivatives also show favorable predicted pharmacokinetic profiles, supporting their potential as orally active antidiabetic agents, although systematic pharmacokinetic evaluation across the class remains limited. This review summarizes recent advances in oxadiazole derivatives as α-glucosidase and α-amylase inhibitors, with emphasis on structure activity relationships (SAR), molecular interactions, and mechanisms of enzyme inhibition. Relevant studies published between 2016 and 2024 were identified through a systematic search of PubMed, Scopus, Web of Science, ScienceDirect, and Google Scholar. The reviewed derivatives showed IC values ranging from 0.07 to 215 μM against α-glucosidase and from 10.60 to 92.16 μM against α-amylase, with several compounds substantially more potent than their corresponding reference inhibitors. Collectively, these findings position the oxadiazole scaffold as a promising framework for the rational design and optimization of next-generation antidiabetic agents.
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5. Bioactivation and reactivity research advances - 2025 year in review.
5. 生物活化与反应性研究进展——2025年度回顾PMID:日期:2026-07-29This year marks the fifth installment of the annual review on bioactivation and reactivity. This series evolved from the broader biotransformation and bioactivation review that started a decade ago, reflecting the increasing importance and interest in this area for drug discovery and development. This year's review features 19 articles that reflect the latest findings and advances in bioactivation and reactivity research. This collection of articles is organized into four general themes: (1) mechanistic insights into CYP-mediated bioactivation, enzyme inhibition, and covalent binding, (2) non-CYP-mediated bioactivation, (3) biological drivers of drug-induced toxicity, and (4) advancements in reactive metabolite trapping.
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6. Humanized mouse models for drug metabolism and drug transport: a systematic review.
6. 药物代谢和药物转运的人源化小鼠模型：一项系统综述PMID:日期:2026-07-09[中文摘要] 动物模型常用于预测人体药代动力学（PK）；然而，由于物种差异，将数据转化为临床结局往往面临挑战。嵌合体和转基因形式的人源化小鼠越来越多地被提出作为药物开发过程中转化性临床前研究的更好工具。因此，本系统综述旨在评估人源化小鼠在人体药物代谢和转运方面的实用性和预测价值。检索的数据库为PubMed、Scopus、Web of Science和Google Scholar。纳入标准为使用经药物代谢酶和/或药物转运体和/或核受体人源化的健康小鼠的研究；以英文发表的、开展人体药物转运/代谢实验性预测的原创研究。共纳入78项研究，提取的数据包括实验分组和动物数量；物种和性别；用于对小鼠进行基因修饰的方法；PK数据；药物-药物相互作用（DDI）预测及相关性。讨论和结论依赖于结果的描述性总结。嵌合模型在数据集中占主导地位，尤其是在PK和代谢物谱研究中，而转基因小鼠则更多与DDI研究相关。两种模型类型均显示出对PK和DDI的良好预测价值，而嵌合小鼠再现了人类代谢途径，识别出传统啮齿动物模型中不存在的人类特异性代谢物。因此，本系统综述表明，用于药物代谢和药物转运的人源化小鼠模型是支持预测临床结局的有用工具，同时应认识到预测效用因模型类型和研究背景而异。
[英文摘要] Animal models are commonly used for prediction of human pharmacokinetics (PKs); however, due to species differences, there are often challenges in translation of the data to clinical outcomes. Humanized mice in the form of chimeric and transgenic models are increasingly proposed as better tools for translational preclinical studies during drug development. Therefore, the aim of this systematic review was to assess the utility and predictive value of humanized mice for human drug metabolism and transport. The databases searched were PubMed, Scopus, Web of Science, and Google Scholar. The inclusion criteria were studies using healthy mice humanized with drug metabolizing enzyme and/or drug transporter and/or nuclear receptors; in original research studies undertaking experimental prediction of human drug transport/metabolism published in the English language. A total of 78 studies were identified and data extracted included experimental groups and number of animals; species and sex; method used to genetically modify the mice; PK data; drug-drug interaction (DDI) predictions and correlations. Discussions and conclusions relied on descriptive summary of results. Chimeric models predominated within the dataset, particularly in PK and metabolite profiling investigations, whereas transgenic mice were more associated with DDI studies. Both model types showed good predictive value for PK and DDIs while chimeric mice replicated human metabolic pathways, identifying human-specific metabolites absent in conventional rodent models. Therefore, this systematic review demonstrates humanized mouse models for drug metabolism and drug transport as useful tools to support prediction of clinical outcomes while recognizing variability in predictive utility across model types and study contexts.
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7. Drug transporters in drug disposition - highlights from the year 2025.
7. 药物转运体在药物处置中的作用——2025年度亮点PMID:日期:2026-07-02On behalf of my co-authors, I am pleased to present our sixth annual review highlighting articles that have been deemed as impactful in the field of drug transporter sciences. Drug transporters influence the absorption, distribution, and elimination of prescribed drugs and, as a result, it is necessary to understand their impact on new drug development programs. The articles highlighted in this review were selected based on their scientific impact, novelty, and relevance to advancing key areas of transporter research, including mechanistic understanding, translational application, and implications for drug development and regulatory science.Similar to our previous reviews, each co-author has selected peer-reviewed articles and provided a brief synopsis of the article and commentary on the article's significance (Chothe et al. 2021,2022,2023,2024; Sandoval et al. 2025). The review is divided into the following sections: (1) transporter function and DDI evaluation, (2) novel models, (3) endogenous biomarkers, and (4) drug transporter structure and regulation. The following synopses and commentaries are meant to provide high-level highlights of the articles and readers are encouraged to review these articles for further details. While individual studies are discussed within these categories, a key objective of this review is to place these findings within broader emerging trends in transporter sciences. The synopsis and commentaries are therefore intended not only to highlight individual studies but also to provide perspective on how these advances collectively shape the field.
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8. Herbal supplements and anti-tuberculosis therapy: unlocking hidden interactions for better multidrug-resistant tuberculosis management.
8. 草药补充剂与抗结核治疗：揭示隐藏的相互作用，优化耐多药结核病管理PMID:日期:2026-06-25Tuberculosis (TB), especially in its multidrug-resistant form (MDR-TB), remains a persistent threat to global health despite decades of medical advancements. Standard treatment regimens often involve complex drug combinations, which, while effective, pose a significant risk of drug-drug interactions (DDIs). The growing reliance on complementary and alternative medicine (CAM), particularly herbal supplements, further complicates this landscape by introducing herb-drug interactions (HDIs), many of which are poorly understood or undocumented. These interactions can compromise treatment efficacy, increase toxicity, and hinder patient adherence, particularly in settings where traditional medicine is widely used. This review emphasizes current evidence on the pharmacological interactions between anti-TB/MDR-TB drugs and other conventional medications, as well as commonly used herbal supplements. We explore the pharmacokinetic and pharmacodynamic mechanisms underlying these interactions, with a focus on cytochrome P450-mediated metabolism and modulation of transporter proteins. Highlighted are key interactions involving TB/MDR-TB medication. In addition, the review discusses the emerging role of Network Pharmacology in mapping multi-target interactions, offering new understandings into the potential risks and benefits of integrating herbal medicine into TB care. The potential therapeutic value of select herbs with hepatoprotective and immunomodulatory properties is critically examined alongside safety concerns. By collating and evaluating findings from clinical, pharmacological, and systems-based research, this review aims to guide healthcare professionals in optimizing TB treatment strategies. Emphasis is placed on the need for proactive monitoring, patient education, and culturally sensitive communication regarding herbal use. Integrating evidence-based approaches with traditional practices could enhance treatment outcomes and minimize adverse effects in TB and MDR-TB management.
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9. Identification and characterization of a novel aldehyde metabolite of WIN18,446 and associated WIN18,446-ALDH1A2 protein adducts using mass spectrometry.
9. 使用质谱法鉴定和表征WIN18,446的一种新型醛代谢物及相关的WIN18,446-ALDH1A2蛋白加合物PMID:日期:2026-06-08ALDH1A family enzymes (ALDH1A1, ALDH1A2, and ALDH1A3) catalyze retinoic acid synthesis, and their dysregulation is linked to disease. Selective inhibitors of these enzymes have been tested in drug discovery programs and one such compound, WIN18,446, was found to irreversibly inhibit ALDH1A2. WIN18,446 is a reversible male contraceptive in humans and animals. The inhibition of spermatogenesis by WIN18,446 is thought to be due to inhibition of ALDH1A. However, the mechanism of irreversible inhibition of ALDH1A2 by WIN18,446 is not known. A crystal structure obtained after incubating ALDH1A2 with WIN18,446 revealed a WIN18,446-derived metabolite covalently adducted to the catalytic cysteine, C320. Inspection of this structure suggested that the observed adduct is unstable and may be a metabolic intermediate stabilized under crystallographic conditions. In the current work, we tested this hypothesis. We identified and characterized an aldehyde metabolite of WIN18,446, which we designated M-54. M-54 is likely the metabolite of the intermediate observed in the crystal structure. Using a range of proteomics techniques, we identified a WIN18,446-derived ALDH1A2 protein adduct of mass 292.07 Da on C319 of ALDH1A2. This adduct may result from the reaction of the crystal structure metabolic intermediate. Using the identified mass, we probed human liver samples from multiple donors and found WIN18,446 specific adducts on cysteines within the ALDH1A1 and ALDH2 active site regions. The current study provides new insight into the metabolism of WIN18,446 and the mechanism of inhibition of ALDH1A2. We also demonstrate a proteomics workflow for identifying and validating drug-protein adducts of unknown mass.