Drug Metabolism Reviews最新文献_第5页

Biotransformation research advances - 2024 year in review. 生物转化研究进展——2024年回顾。

IF 3.8 2区医学

Drug Metabolism Reviews Pub Date : 2025-11-01 Epub Date: 2025-08-13 DOI: 10.1080/03602532.2025.2538676

Lionel Cheruzel, Upendra A Argikar, Pietro Brunetti, Maria Chatzopoulou, Sungjoon Cho, Rachel D Crouch, Deepika Dhaware, Kevin M Johnson, Valerie Kramlinger, Joyce Liu, Bin Ma, Hlaing Maw, Karoline Rehm, Herana Kamal Seneviratne, Lloyd Wei Tat Tang, Guo Zhong, S Cyrus Khojasteh

引用次数: 0

Insights into CYP450 polymorphisms and their impact on drug metabolism in Alzheimer's disease therapy. CYP450多态性及其对阿尔茨海默病治疗中药物代谢的影响

IF 3.8 2区医学

Drug Metabolism Reviews Pub Date : 2025-11-01 Epub Date: 2025-09-03 DOI: 10.1080/03602532.2025.2552786

Jingjing Zheng, Guoqing Liu, Qi Wang, Yong Liang

{"title":"Insights into CYP450 polymorphisms and their impact on drug metabolism in Alzheimer's disease therapy.","authors":"Jingjing Zheng, Guoqing Liu, Qi Wang, Yong Liang","doi":"10.1080/03602532.2025.2552786","DOIUrl":"10.1080/03602532.2025.2552786","url":null,"abstract":"Alzheimer's disease (AD) is a complex neurodegenerative disorder that poses significant therapeutic challenges. Currently available treatments offer symptomatic relief but often yield suboptimal outcomes due to inter-individual variability in drug metabolism. Cytochrome P450 (CYP450) enzymes, particularly those exhibiting genetic polymorphisms, play a central role in the hepatic metabolism of many AD medications. This review focuses on the influence of CYP450 polymorphisms-specifically in CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4-on the pharmacokinetics, efficacy, and safety of approved anti-AD drugs. We discuss how variability in CYP450 expression and activity affects drug response, and examine the implications for adverse drug reactions, therapeutic failure, and dosage optimization. In addition, we evaluate current evidence for CYP450-mediated interactions with traditional Chinese medicines, which are increasingly used in complementary AD therapy. The potential for CYP450 genotyping and phenotyping to guide personalized treatment strategies is critically assessed. We argue that integrating pharmacogenomics into clinical practice may enhance therapeutic precision, reduce adverse outcomes, and improve quality of life in patients with AD. This review provides updated insight into the clinical significance of CYP450 polymorphisms in AD therapy and outlines future directions for personalized medicine approaches.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":" ","pages":"523-534"},"PeriodicalIF":3.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946873","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

Research on the content and activity of CYP450 enzymes in human liver. 人肝脏CYP450酶含量及活性的研究。

IF 3.8 2区医学

Drug Metabolism Reviews Pub Date : 2025-11-01 Epub Date: 2025-10-11 DOI: 10.1080/03602532.2025.2568231

Cunzhen Zhang, Yan Fang, Lin Jia, Hailing Qiao

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 : 2025-11-01 Epub 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":"400-431"},"PeriodicalIF":3.8,"publicationDate":"2025-11-01","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

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 3.8 2区医学

Drug Metabolism Reviews Pub Date : 2025-11-01 Epub 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":"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":"311-337"},"PeriodicalIF":3.8,"publicationDate":"2025-11-01","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

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 : 2025-11-01 Epub 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

Correction. 修正。

IF 3.8 2区医学

Drug Metabolism Reviews Pub Date : 2025-11-01 Epub Date: 2025-08-28 DOI: 10.1080/03602532.2025.2552600

引用次数: 0

Preface to DMR drug-drug interactions special issue. DMR药物-药物相互作用特刊前言。

IF 3.8 2区医学

Drug Metabolism Reviews Pub Date : 2025-08-01 Epub Date: 2025-09-08 DOI: 10.1080/03602532.2024.2351756

Robert S Foti

引用次数: 0

Enzyme-mediated drug-drug interactions: a review of in vivo and in vitro methodologies, regulatory guidance, and translation to the clinic. 酶介导的药物间相互作用：体内和体外方法、监管指南和临床转化综述。

IF 3.8 2区医学

Drug Metabolism Reviews Pub Date : 2025-08-01 Epub Date: 2024-07-26 DOI: 10.1080/03602532.2024.2381021

Jaydeep Yadav, Benjamin J Maldonato, Joseph M Roesner, Ana G Vergara, Erickson M Paragas, Theresa Aliwarga, Sara Humphreys

{"title":"Enzyme-mediated drug-drug interactions: a review of in vivo and in vitro methodologies, regulatory guidance, and translation to the clinic.","authors":"Jaydeep Yadav, Benjamin J Maldonato, Joseph M Roesner, Ana G Vergara, Erickson M Paragas, Theresa Aliwarga, Sara Humphreys","doi":"10.1080/03602532.2024.2381021","DOIUrl":"10.1080/03602532.2024.2381021","url":null,"abstract":"Enzyme-mediated pharmacokinetic drug-drug interactions can be caused by altered activity of drug metabolizing enzymes in the presence of a perpetrator drug, mostly via inhibition or induction. We identified a gap in the literature for a state-of-the art detailed overview assessing this type of DDI risk in the context of drug development. This manuscript discusses in vitro and in vivo methodologies employed during the drug discovery and development process to predict clinical enzyme-mediated DDIs, including the determination of clearance pathways, metabolic enzyme contribution, and the mechanisms and kinetics of enzyme inhibition and induction. We discuss regulatory guidance and highlight the utility of in silico physiologically-based pharmacokinetic modeling, an approach that continues to gain application and traction in support of regulatory filings. Looking to the future, we consider DDI risk assessment for targeted protein degraders, an emerging small molecule modality, which does not have recommended guidelines for DDI evaluation. Our goal in writing this report was to provide early-career researchers with a comprehensive view of the enzyme-mediated pharmacokinetic DDI landscape to aid their drug development efforts.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":" ","pages":"211-243"},"PeriodicalIF":3.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757724","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

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