Drug Metabolism Reviews最新文献

{"title":"Analytical Techniques for Methyldopa and Metabolites: A Comprehensive Review.","authors":"Hemn A H Barzani, Seerwan Hamadameen Sulaiman, Rebaz Anwar Omer, Ali Hussein Mer, Hoshyar Saadi Ali","doi":"10.1080/03602532.2025.2560487","DOIUrl":"https://doi.org/10.1080/03602532.2025.2560487","url":null,"abstract":"<p><p>Methyldopa, a centrally acting α2-adrenergic agonist, remains a key antihypertensive drug, particularly prescribed for pregnant and renal-impaired patients. Its clinical significance has led to extensive research aimed at developing reliable analytical methods for its accurate, sensitive, and selective determination in pharmaceutical formulations and biological matrices. Relevant literature was retrieved from Scopus, Web of Science, ScienceDirect, PubMed, and Google Scholar, restricted to English-language publications. This review critically examines the diverse analytical approaches used for Methyldopa quantification, outlining their principles, advantages, limitations, and applicability in both advanced and resource-limited settings. Chromatographic methods, especially high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS/MS), remain the most robust techniques, offering excellent sensitivity (LOD: 10-50 ng/mL for HPLC; as low as 0.7-15 ng/mL for LC-MS/MS) with rapid analysis times. While LC-MS/MS provides superior detection, it is limited by high costs and technical expertise requirements. Electrochemical methods, particularly voltammetry, stand out for their affordability, rapid analysis, and feasibility in decentralized laboratories, achieving LOD values as low as 0.01-0.05 µM. Spectrophotometric approaches, primarily UV-Vis, remain the simplest and most cost-effective options, making them useful for routine quality control, though with reduced selectivity and higher detection limits. Key analytical challenges include Methyldopa's low concentration in biological fluids, chemical instability, and matrix interferences. This review provides a comparative evaluation of chromatographic, spectrophotometric, and electrochemical techniques, emphasizing the need for portable, low-cost platforms to expand accessibility in therapeutic monitoring. Overall, it offers critical insights for advancing Methyldopa analysis and improving clinical management in diverse healthcare settings.</p>","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":" ","pages":"1-60"},"PeriodicalIF":3.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033078","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}

{"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":"https://doi.org/10.1080/03602532.2025.2552786","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":" ","pages":"1-12"},"PeriodicalIF":3.8,"publicationDate":"2025-09-03","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}

{"title":"Cyclodextrins grafted magnetite (Fe₃O₄) nanocarriers for anticancer therapy.","authors":"Sivakumar Krishnamoorthy, Divya Annaparvathi Suyamburaj","doi":"10.1080/03602532.2025.2549294","DOIUrl":"https://doi.org/10.1080/03602532.2025.2549294","url":null,"abstract":"<p><p>This comprehensive review explores the therapeutic promise of cyclodextrin-grafted magnetite (Fe₃O₄) nanocarriers in anticancer applications, focusing on their design, drug delivery mechanisms, biological stability, and therapeutic performance. Systems integrating cyclodextrins (cds) with Fe₃O₄ nanoparticles (Fe₃O₄-cd-drug) have been developed for delivery of key anticancer agents such as docetaxel, irinotecan, paclitaxel, and doxorubicin across 11 cancer cell types. Results demonstrate up to 60% reduced cancer cell viability when using magnetite nanoparticle (Fe₃O₄-np)-cds-docetaxel/irinotecan/doxorubicin systems compared to the pristine drug. cd grafting enhances nanoparticle hydrophilicity, drug encapsulation, colloidal stability, and biocompatibility, enabling sustained and targeted drug release. Direct grafting of cds onto Fe₃O₄ yields superior cytotoxicity of 93% death of epidermoid carcinoma (A431) cells with Fe₃O₄-np-cds-irinotecan system compared to linker-mediated systems. In the case of Fe₃O₄-np-cds-doxorubicin system tested on human breast cancer cell (MCF-7) cells shows 38% cell death and adding hyperthermia kills 30% of cells. Compared to alternative grafting like polyethylene glycol (PEG), poly(lactic-co-glycolic acid) (PLGA), metal-organic frameworks (MOFs), or carbon-based materials, cds offer unique advantages including Food and Drug Administration (FDA)-approved biocompatibility, pH-sensitive release, and support for combination therapies. Cluster analysis categorized Fe₃O₄-cd-drug systems based on cytotoxic efficiency and drug concentration, identifying structure-function relationships and highlighting the superiority of systems with multimodal surface engineering. Mechanistic insights reveal endocytosis-mediated uptake, lysosomal-triggered drug release, reactive oxygen species (ROS) generation via Fenton-like reactions, and enhanced cytotoxicity under hyperthermia. Despite these advances, gaps remain in understanding inclusion complex chemistry, biodistribution, and structure-activity relationships. This review highlights the potential of Fe₃O₄-np-cds-drug systems and emphasizes the urgent need for systematic molecular and material-level studies to optimize Fe₃O₄-cd-drug systems for translational cancer therapy.</p>","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":" ","pages":"1-18"},"PeriodicalIF":3.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946816","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}

{"title":"Correction.","authors":"","doi":"10.1080/03602532.2025.2552600","DOIUrl":"https://doi.org/10.1080/03602532.2025.2552600","url":null,"abstract":"","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":" ","pages":"1"},"PeriodicalIF":3.8,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946877","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}

{"title":"Biotransformation research advances - 2024 year in review.","authors":"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","doi":"10.1080/03602532.2025.2538676","DOIUrl":"10.1080/03602532.2025.2538676","url":null,"abstract":"<p><p>This is the ninth installment of this annual review. In line with previous years, the primary objective is to highlight articles deemed by us of significant interest in the broad field of biotransformation. Sixteen manuscripts have been collated and presented herein accompanied by a synopsis, commentary and relevant figures. This year's collection delves into five main areas: (1) the metabolism and disposition of various investigative and approved drugs, (2) non-CYP enzymatic biotransformation, (3) novel models and approaches, (4) the role of gut microbiota, and (5) modulating drug-metabolizing enzyme activities.</p>","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":" ","pages":"1-35"},"PeriodicalIF":3.8,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706788","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}

{"title":"Metabolism of new drug modalities research advances - 2024 year in review.","authors":"Bin Ma, Upendra A Argikar, Luying Chen, Lionel Cheruzel, Sungjoon Cho, Ting-Jia Gu, Simon Hauri, Valerie M Kramlinger, Xiuli Li, Joyce Liu, Simone Schadt, Herana Kamal Seneviratne, Rachel Liuqing Shi, Lloyd Wei Tat Tang, Donglu Zhang, Guo Zhong, S Cyrus Khojasteh","doi":"10.1080/03602532.2025.2542220","DOIUrl":"10.1080/03602532.2025.2542220","url":null,"abstract":"<p><p>New drug modalities (NDMs) have gained significant popularity and attention in recent years due to their ability to target previously undruggable pathways and offer new strategies for tackling complex diseases. This trend is reflected in our review, which encompasses 17 publications, an increase from 11 last year and includes a growing number of contributors across industry and academia. We have focused on five categories of NDMs: (1) Peptides with an emphasis on macrocyclic structures; (2) Bivalent protein degraders, also known as proteolysis-targeting chimeras (PROTACs); (3) Conjugated drugs, including peptide-drug and antibody-drug conjugates; (4) Antisense oligonucleotides and <i>N</i>-acetylgalactosamine (GalNAc) conjugated oligonucleotides; and (5) Covalent inhibitors.</p>","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":" ","pages":"1-38"},"PeriodicalIF":3.8,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774926","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}

{"title":"Preface to DMR drug-drug interactions special issue.","authors":"Robert S Foti","doi":"10.1080/03602532.2024.2351756","DOIUrl":"https://doi.org/10.1080/03602532.2024.2351756","url":null,"abstract":"","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":"57 3","pages":"208-210"},"PeriodicalIF":3.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014170","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}

{"title":"Enzyme-mediated drug-drug interactions: a review of <i>in vivo</i> and <i>in vitro</i> 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":"<p><p>Enzyme-mediated pharmacokinetic drug-drug interactions can be caused by altered activity of drug metabolizing enzymes in the presence of a perpetrator drug, mostly <i>via</i> 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 <i>in vitro</i> and <i>in vivo</i> 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 <i>in silico</i> 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.</p>","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}

{"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":"<p><p>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 <i>in vitro</i> 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.</p>","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}

{"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":"<p><p>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, <i>in vitro</i>/<i>in vivo</i> 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 <i>in vitro</i> evaluation, 2) novel <i>in vitro</i>/<i>in vivo</i> 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.</p>","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}