Drug Metabolism Reviews最新文献_第2页

Assessing and mitigating pH-mediated DDI risks in drug development - formulation approaches and clinical considerations. 在药物开发过程中评估和减轻 pH 值介导的 DDI 风险--制剂方法和临床考虑因素。

IF 3.8 2区医学

Drug Metabolism Reviews Pub Date : 2025-08-01 Epub Date: 2024-05-03 DOI: 10.1080/03602532.2024.2345632

Di Wu, Jiaying Liu, Erickson M Paragas, Jaydeep Yadav, Theresa Aliwarga, Tycho Heimbach, M Sebastian Escotet-Espinoza

{"title":"Assessing and mitigating pH-mediated DDI risks in drug development - formulation approaches and clinical considerations.","authors":"Di Wu, Jiaying Liu, Erickson M Paragas, Jaydeep Yadav, Theresa Aliwarga, Tycho Heimbach, M Sebastian Escotet-Espinoza","doi":"10.1080/03602532.2024.2345632","DOIUrl":"10.1080/03602532.2024.2345632","url":null,"abstract":"pH-mediated drug-drug interactions (DDI) is a prevalent DDI in drug development, especially for weak base compounds with highly pH-dependent solubility. FDA has released a guidance on the evaluation of pH-mediated DDI assessments using in vitro testing and clinical studies. Currently, there is no common practice of ways of testing across the academia and industry. The development of biopredictive method and physiologically-based biopharmaceutics modeling (PBBM) approaches to assess acid-reducing agent (ARA)-DDI have been proven with accurate prediction and could decrease drug development burden, inform clinical design and potentially waive clinical studies. Formulation strategies and careful clinical design could help mitigate the pH-mediated DDI to avoid more clinical studies and label restrictions, ultimately benefiting the patient. In this review paper, a detailed introduction on biorelevant dissolution testing, preclinical and clinical study requirement and PBPK modeling approaches to assess ARA-DDI are described. An improved decision tree for pH-mediated DDI is proposed. Potential mitigations including clinical or formulation strategies are discussed.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":" ","pages":"291-310"},"PeriodicalIF":3.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140848144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Drug transporters in drug disposition - highlights from the year 2024. 药物处置中的药物转运体——以2024年为例。

IF 3.8 2区医学

Drug Metabolism Reviews Pub Date : 2025-08-01 DOI: 10.1080/03602532.2025.2537399

Philip Sandoval, Pallabi Mitra, Upendra A Argikar, Masanori Nakakariya, Diane Ramsden, Charles J Rotter, Kimio Tohyama, Paresh P Chothe

{"title":"Drug transporters in drug disposition - highlights from the year 2024.","authors":"Philip Sandoval, Pallabi Mitra, Upendra A Argikar, Masanori Nakakariya, Diane Ramsden, Charles J Rotter, Kimio Tohyama, Paresh P Chothe","doi":"10.1080/03602532.2025.2537399","DOIUrl":"10.1080/03602532.2025.2537399","url":null,"abstract":"On behalf of my coauthors, I am pleased to present our fifth annual review highlighting articles in the field of drug transporters that have been deemed as influential. The field of drug-transporters is rapidly evolving with new transporter structure data, in vitro/in vivo models in addition to clinical tools being applied to better understand their role in drug disposition. Each coauthor has selected peer-reviewed articles from the year 2024 and provided a brief summary with a commentary, as done in our previous reviews. (Chothe et al. 2021, 2022,2023, 2024). The review is divided into the following sections based on the selected articles: 1) transporter structure and in vitro evaluation, 2) novel in vitro/in vivo models, 3) endogenous biomarkers and 4) drug transporters and toxicity. As these commentaries are meant to provide brief highlights of the articles, readers are encouraged to consult the original articles for further details. I would also like to thank my coauthors for their work and dedication to this review over the years.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":" ","pages":"1-32"},"PeriodicalIF":3.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transporter-mediated drug-drug interactions: regulatory guidelines, in vitro and in vivo methodologies and translation, special populations, and the blood-brain barrier. 转运体介导的药物间相互作用：监管指南、体外和体内方法及转化、特殊人群和血脑屏障。

IF 3.8 2区医学

Drug Metabolism Reviews Pub Date : 2025-08-01 Epub Date: 2024-07-05 DOI: 10.1080/03602532.2024.2364591

Laura E Russell, Jaydeep Yadav, Benjamin J Maldonato, Huan-Chieh Chien, Ling Zou, Ana G Vergara, Erick G Villavicencio

{"title":"Transporter-mediated drug-drug interactions: regulatory guidelines, in vitro and in vivo methodologies and translation, special populations, and the blood-brain barrier.","authors":"Laura E Russell, Jaydeep Yadav, Benjamin J Maldonato, Huan-Chieh Chien, Ling Zou, Ana G Vergara, Erick G Villavicencio","doi":"10.1080/03602532.2024.2364591","DOIUrl":"10.1080/03602532.2024.2364591","url":null,"abstract":"This review, part of a special issue on drug-drug interactions (DDIs) spearheaded by the International Society for the Study of Xenobiotics (ISSX) New Investigators, explores the critical role of drug transporters in absorption, disposition, and clearance in the context of DDIs. Over the past two decades, significant advances have been made in understanding the clinical relevance of these transporters. Current knowledge on key uptake and efflux transporters that affect drug disposition and development is summarized. Regulatory guidelines from the FDA, EMA, and PMDA that inform the evaluation of potential transporter-mediated DDIs are discussed in detail. Methodologies for preclinical and clinical testing to assess potential DDIs are reviewed, with an emphasis on the utility of physiologically based pharmacokinetic (PBPK) modeling. This includes the application of relative abundance and expression factors to predict human pharmacokinetics (PK) using preclinical data, integrating the latest regulatory guidelines. Considerations for assessing transporter-mediated DDIs in special populations, including pediatric, hepatic, and renal impairment groups, are provided. Additionally, the impact of transporters at the blood-brain barrier (BBB) on the disposition of CNS-related drugs is explored. Enhancing the understanding of drug transporters and their role in drug disposition and toxicity can improve efficacy and reduce adverse effects. Continued research is essential to bridge remaining gaps in knowledge, particularly in comparison with cytochrome P450 (CYP) enzymes.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":" ","pages":"244-271"},"PeriodicalIF":3.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Insights into pharmacogenetics, drug-gene interactions, and drug-drug-gene interactions. 对药物遗传学、药物-基因相互作用以及药物-药物-基因相互作用的见解。

IF 3.8 2区医学

Drug Metabolism Reviews Pub Date : 2025-08-01 Epub Date: 2024-08-18 DOI: 10.1080/03602532.2024.2385928

Laura E Russell, Katrina G Claw, Kaja M Aagaard, Sarah M Glass, Kuheli Dasgupta, F Leah Nez, Alex Haimbaugh, Benjamin J Maldonato, Jaydeep Yadav

{"title":"Insights into pharmacogenetics, drug-gene interactions, and drug-drug-gene interactions.","authors":"Laura E Russell, Katrina G Claw, Kaja M Aagaard, Sarah M Glass, Kuheli Dasgupta, F Leah Nez, Alex Haimbaugh, Benjamin J Maldonato, Jaydeep Yadav","doi":"10.1080/03602532.2024.2385928","DOIUrl":"10.1080/03602532.2024.2385928","url":null,"abstract":"This review explores genetic contributors to drug interactions, known as drug-gene and drug-drug-gene interactions (DGI and DDGI, respectively). This article is part of a mini-review issue led by the International Society for the Study of Xenobiotics (ISSX) New Investigators Group. Pharmacogenetics (PGx) is the study of the impact of genetic variation on pharmacokinetics (PK), pharmacodynamics (PD), and adverse drug reactions. Genetic variation in pharmacogenes, including drug metabolizing enzymes and drug transporters, is common and can increase the risk of adverse drug events or contribute to reduced efficacy. In this review, we summarize clinically actionable genetic variants, and touch on methodologies such as genotyping patient DNA to identify genetic variation in targeted genes, and deep mutational scanning as a high-throughput in vitro approach to study the impact of genetic variation on protein function and/or expression in vitro. We highlight the utility of physiologically based pharmacokinetic (PBPK) models to integrate genetic and chemical inhibitor and inducer data for more accurate human PK simulations. Additionally, we analyze the limitations of historical ethnic descriptors in pharmacogenomics research. Altogether, the work herein underscores the importance of identifying and understanding complex DGI and DDGIs with the intention to provide better treatment outcomes for patients. We also highlight current barriers to wide-scale implementation of PGx-guided dosing as standard or care in clinical settings.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":" ","pages":"272-290"},"PeriodicalIF":3.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction. 修正。

IF 3.8 2区医学

Drug Metabolism Reviews Pub Date : 2025-07-30 DOI: 10.1080/03602532.2025.2541147

引用次数: 0

Bioactivation and reactivity research advances-2024 year in review. 生物活性和反应性研究进展- 2024年综述。

IF 3.8 2区医学

Drug Metabolism Reviews Pub Date : 2025-07-28 DOI: 10.1080/03602532.2025.2530407

Joyce Liu, Upendra A Argikar, Pietro Brunetti, Maria Chatzopoulou, Luying Chen, Sungjoon Cho, Simon Hauri, Valerie Kramlinger, Jakob Lang, Bin Ma, Karoline Rehm, Herana Kamal Seneviratne, Lloyd Wei Tat Tang, John C Tran, Guo Zhong, S Cyrus Khojasteh

引用次数: 0

Traditional Chinese medicine and gut microbiota: biotransformation, interaction, and implications for chronic disease treatment. 中医药与肠道菌群：生物转化、相互作用及其对慢性疾病治疗的影响。

IF 3.4 2区医学

Drug Metabolism Reviews Pub Date : 2025-07-09 DOI: 10.1080/03602532.2025.2520768

Xia Hao, Jinbo Zhang, Ruishuang Ma, Bin Yao, Wei Yang

{"title":"Traditional Chinese medicine and gut microbiota: biotransformation, interaction, and implications for chronic disease treatment.","authors":"Xia Hao, Jinbo Zhang, Ruishuang Ma, Bin Yao, Wei Yang","doi":"10.1080/03602532.2025.2520768","DOIUrl":"10.1080/03602532.2025.2520768","url":null,"abstract":"The gut microbiota (GM), often regarded as a vital 'functional organ,' plays a crucial role in human physiological processes. GM is involved in substance metabolism, especially the biotransformation of pharmaceuticals. It modulates drug pharmacological activity and bioavailability through various metabolic pathways. Since traditional Chinese medicine (TCM) is primarily administered orally, its active compounds inevitably interact with the GM. This review systematically explores the bidirectional interplay between TCM and GM. GM metabolizes TCM components via enzymatic reactions (e.g. hydrolysis, reduction, and deconjugation) and interactions with metabolites, thereby enhancing bioavailability and sometimes modifying pharmacological properties. Conversely, TCM influences GM composition and function by promoting beneficial taxa, restoring microbial balance, and regulating microbial metabolites such as short-chain fatty acids and bile acids. The TCM-GM interaction shows promise in treating chronic diseases, such as inflammatory bowel disease, mental disorders, and cardiovascular diseases. However, challenges remain in fully understanding these interactions due to the complexity of TCM formulations and individual variations in GM composition. Future research should employ multi-omics approaches to develop personalized TCM therapies based on individual GM profiles.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":" ","pages":"1-24"},"PeriodicalIF":3.4,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An in-depth review of PPARγ modulators as anti-diabetes therapeutics. PPARγ调节剂作为抗糖尿病治疗药物的深入综述。

IF 3.4 2区医学

Drug Metabolism Reviews Pub Date : 2025-05-23 DOI: 10.1080/03602532.2025.2508152

Aryan Jangra, Basuvan Babu, Selvaraj Divakar, Byran Gowramma, Saveri Rajan, Sonam Jangra, Vishnu Malakar

{"title":"An in-depth review of PPARγ modulators as anti-diabetes therapeutics.","authors":"Aryan Jangra, Basuvan Babu, Selvaraj Divakar, Byran Gowramma, Saveri Rajan, Sonam Jangra, Vishnu Malakar","doi":"10.1080/03602532.2025.2508152","DOIUrl":"https://doi.org/10.1080/03602532.2025.2508152","url":null,"abstract":"Drug metabolism and pharmacokinetics (DMPK) plays a crucial role in optimizing peroxisome proliferator-activated receptor gamma (PPARγ) modulators by influencing metabolism, therapeutic efficacy, and safety. Rosiglitazone is primarily metabolized by cytochrome 2C8 (CYP2C8) and CYP2C9, with the CYP2C83 polymorphism increasing clearance, reducing efficacy, and altering fluid retention. Troglitazone metabolism via CYP3A4 and CYP2C8 generates a reactive quinone metabolite, depleting glutathione (GSH), elevating mitochondrial oxidative stress, and inducing hepatotoxicity. Glitazones also undergo GSH conjugation through open-ring formation, influencing detoxification and toxicity. Inflammation downregulates CYP enzymes and transporters, altering drug clearance and increasing drug-drug interaction (DDI) risks. Ketoconazole and troleandomycin inhibit rosiglitazone metabolism by 52% and 40%, respectively, while pioglitazone inhibits CYP2C8-mediated arachidonic acid metabolism, impairing renal function. Gemfibrozil further increases pioglitazone's area under the curve (AUC) threefold by inhibiting CYP2C8. Additionally, rosiglitazone modulates OATP1B1, enhancing pravastatin uptake at low concentrations but inhibiting it at higher levels, affecting plasma levels. Troglitazone inhibits organic anion-transporting polypeptide 1B1 (OATP1B1) mediated rosuvastatin uptake, reducing hepatic delivery and efficacy, necessitating strategic drug combinations. Furthermore, new PPARγ modulators are being developed via selective and partial activation to mitigate toxicity, incorporating non-thiazolidinedione scaffolds and optimizing DMPK properties through nanocarriers such as lipid-based nanoparticles. A deeper understanding of these factors is essential for designing next-generation PPARγ-targeted therapeutics, ensuring improved efficacy, reduced toxicity, and enhanced suitability for personalized medicine.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":" ","pages":"1-27"},"PeriodicalIF":3.4,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Metabolism of m-CPP, trazodone, nefazodone, and etoperidone: clinical and forensic aspects. m-CPP、曲唑酮、奈法唑酮和依托哌啶酮的代谢：临床和法医方面。

IF 3.8 2区医学

Drug Metabolism Reviews Pub Date : 2025-05-01 Epub Date: 2025-02-20 DOI: 10.1080/03602532.2025.2465482

Mariana Duarte Costa Alegre, Daniel José Barbosa, Ricardo Jorge Dinis-Oliveira

{"title":"Metabolism of m-CPP, trazodone, nefazodone, and etoperidone: clinical and forensic aspects.","authors":"Mariana Duarte Costa Alegre, Daniel José Barbosa, Ricardo Jorge Dinis-Oliveira","doi":"10.1080/03602532.2025.2465482","DOIUrl":"10.1080/03602532.2025.2465482","url":null,"abstract":"Trazodone, nefazodone, and etoperidone are classified as atypical antidepressants belonging to the phenylpiperazine class. These antidepressants are primarily metabolized by CYP3A4 into m-chlorophenylpiperazine (mCPP), which was initially employed in veterinary medicine but has gained widespread use as a recreational drug globally despite legal restrictions in numerous countries. The active metabolite, mCPP, exerts various neuropsychiatric effects by interacting with serotonin receptors. It primarily exhibits nonselective agonistic properties with some antagonistic effects and influences temperature, behavior, and hormone release via central 5-HT receptors. The surge in mCPP popularity can be attributed to its MDMA-like effects, and its initial misidentification as an MDMA substitute facilitated its unregulated distribution worldwide. This review aims to comprehensively explore the pharmacokinetics and pharmacodynamics of these compounds, with a specific focus on the forensic challenges posed by mCPP as a metabolite of antidepressants. The primary objective is to delineate the consumption patterns of these compounds in laboratory settings, making this review crucial for understanding the intricate nuances of these drugs in forensic contexts.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":" ","pages":"115-146"},"PeriodicalIF":3.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Scaling factors to inform in vitro-in vivo extrapolation from preclinical and livestock animals: state of the field and recommendations for development of missing data. 从临床前和家畜进行体内外推的比例因子：领域现状和缺失数据的发展建议。

IF 3.8 2区医学

Drug Metabolism Reviews Pub Date : 2025-05-01 Epub Date: 2025-02-24 DOI: 10.1080/03602532.2025.2462527

Austin A Zimmer, Abby C Collier

{"title":"Scaling factors to inform in vitro-in vivo extrapolation from preclinical and livestock animals: state of the field and recommendations for development of missing data.","authors":"Austin A Zimmer, Abby C Collier","doi":"10.1080/03602532.2025.2462527","DOIUrl":"10.1080/03602532.2025.2462527","url":null,"abstract":"The use of in-vitro-in-vivo physiologically based pharmacokinetic (IVIVE-PBPK) modeling approaches assists for prediction of first-in animal or human trials. These approaches are underpinned by the scaling factors: microsomal protein per gram (MPPG) and cytosolic protein per gram (CPPG). In addition, IVIVE-PBPK has significant application in the reduction and refinement of live animal models in research. While human scaling factors are well-defined, many preclinical and livestock species remain poorly elucidated or uncharacterized. The MPPG parameter for liver (MPPGL) is the best characterized across all species and is well-defined for mouse, rat, and dog models. The MPPG parameters for Kidney (MPPGK) and intestine (MPPGI), are however; relatively indefinite for most species. Similarly, CPPG scaling factors for liver, kidney, and intestine (CPPGL/CPPGK/CPPGI) are generally sparse in all species. In addition to generation of mathematical values for scaling factors, methodological and animal-specific considerations, such as age, sex, and strain differences, have not yet been comprehensively described. Here, we review the current state-of-the-field for microsomal and cytosolic scaling factors, including highlighting areas that may need further description and development, with the intention of drawing attention to key knowledge gaps. The intention is to promote improved accuracy and precision in IVIVE-PBPK, concordance between laboratories, and stimulate work in underserved, but increasingly vital areas.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":" ","pages":"91-114"},"PeriodicalIF":3.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0