Drug Metabolism Reviews最新文献

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 3.4 2区医学

Drug Metabolism Reviews Pub Date : 2025-07-11 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 3.4 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":3.4,"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 3.4 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":3.4,"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

In-depth understanding of the structure-based reactive metabolite formation of organic functional groups. 基于结构的有机官能团反应性代谢物形成的深入理解。

IF 3.4 2区医学

Drug Metabolism Reviews Pub Date : 2025-05-01 Epub Date: 2025-03-05 DOI: 10.1080/03602532.2025.2472076

Chunyong He, Yuchang Mao, Hong Wan

{"title":"In-depth understanding of the structure-based reactive metabolite formation of organic functional groups.","authors":"Chunyong He, Yuchang Mao, Hong Wan","doi":"10.1080/03602532.2025.2472076","DOIUrl":"10.1080/03602532.2025.2472076","url":null,"abstract":"Idiosyncratic drug-induced liver injury (DILI) is a leading cause of drug attrition and/or withdrawal. The formation of reactive metabolites is widely accepted as a key factor contributing to idiosyncratic DILI. Therefore, identifying reactive metabolites has become a critical focus during lead optimization, and a combination of GSH-/cyano-trapping and cytochrome P450 inactivation studies is recommended to identify compounds with the potential to generate reactive metabolites. Daily dose, clinical indication, detoxication pathways, administration route, and treatment duration are the most considerations when deprioritizing candidates that generate reactive metabolites. Removing the structural alerts is considered a pragmatic strategy for mitigating the risk associated with reactive metabolites, although this approach may sometimes exclude otherwise potent molecules. In this context, an in-depth insight into the structure-based reactive metabolite formation of organic functional groups can significantly aid in the rational design of drug candidates with improved safety profiles. The primary goal of this review is to delve into an analysis of the bioactivation mechanisms of organic functional groups and their potential detrimental effects with recent examples to assist medicinal chemists and metabolism scientists in designing safer drug candidates with a higher likelihood of success.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":" ","pages":"147-189"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499708","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

Genetic determinants of paclitaxel-induced peripheral neuropathy: a review of current literature. 紫杉醇诱导周围神经病变的遗传决定因素：当前文献综述。

IF 3.4 2区医学

Drug Metabolism Reviews Pub Date : 2025-05-01 Epub Date: 2025-03-31 DOI: 10.1080/03602532.2025.2485055

Swathi Krishna Sivadas, Aiswarya Das, Nandana Vijayakumar, Nandana Shaji, Sabitha Mangalath, Keechilat Pavithran, Lalitha Biswas

{"title":"Genetic determinants of paclitaxel-induced peripheral neuropathy: a review of current literature.","authors":"Swathi Krishna Sivadas, Aiswarya Das, Nandana Vijayakumar, Nandana Shaji, Sabitha Mangalath, Keechilat Pavithran, Lalitha Biswas","doi":"10.1080/03602532.2025.2485055","DOIUrl":"10.1080/03602532.2025.2485055","url":null,"abstract":"Paclitaxel is a widely used chemotherapeutic agent recognized for its efficacy against various malignancies. However, its clinical utility is often limited by paclitaxel-induced peripheral neuropathy (PIPN), a dose-dependent and debilitating side effect that significantly impacts patient quality of life. Genetic predisposition plays a critical role in individual susceptibility to PIPN, influencing both drug metabolism and neuropathic responses. This review examines the genetic basis of PIPN, focusing on polymorphisms in key genes associated with paclitaxel metabolism, transport, neuroinflammation, and neuronal signaling. Variants in CYP2C8, CYP3A4, and CYP2C9 affect drug metabolism, while polymorphisms in ABCB1 and SLCO1B1 influence drug transport. Genes involved in neuroinflammatory pathways (TNF-α, IL-6, IL-1β), peripheral nerve integrity (MAPT, TUBB2), and neuronal signaling (SCN9A) have also been implicated in PIPN susceptibility. Understanding genetic contributions to PIPN is essential for unraveling its pathophysiology and developing targeted interventions. Integrating genetic markers into clinical practice can facilitate personalized treatment strategies, minimizing PIPN risk and enhancing therapeutic outcomes. Further studies are needed to validate these findings across diverse populations and uncover novel genetic determinants.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":" ","pages":"190-207"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751324","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

Herb-drug interaction potential of Astragali Radix: a metabolic perspective. 黄芪的药物相互作用潜力：代谢的观点。

IF 3.4 2区医学

Drug Metabolism Reviews Pub Date : 2025-02-01 Epub Date: 2024-12-18 DOI: 10.1080/03602532.2024.2441235

Tianwang Wang, Xiaofei Chen, Qing Gao, Chonggang Huang, Kai Wang, Feng Qiu

{"title":"Herb-drug interaction potential of Astragali Radix: a metabolic perspective.","authors":"Tianwang Wang, Xiaofei Chen, Qing Gao, Chonggang Huang, Kai Wang, Feng Qiu","doi":"10.1080/03602532.2024.2441235","DOIUrl":"10.1080/03602532.2024.2441235","url":null,"abstract":"Astragali Radix (AR) is one of the most widely used herbs in Asia and has a wide range of biological activities. These activities are attributed to its various compounds like flavonoids, saponins, and polysaccharides. AR and its major components are often used in combination with other drugs for the treatment of diseases such as cancer and cerebral ischemia. With the expanding range of AR combinations, the potential for herb-drug interaction (HDI) has been raised. Key targets in HDI studies include drug-metabolizing enzymes (DMEs) and transporters. Existing studies have shown that AR and its major components have various regulatory effects on these targets, notably CYP2C9, CYP3A4, UGT1A6, and P-gp. AR may contribute to HDI when it is taken with substrates of these biomolecules, such as tolbutamide, midazolam, and digoxin. However, there are also different views in the current study, such as the effect of AR on CYP3A4. To better understand the interactions of AR with drugs, we review the metabolic pathways and pharmacokinetic parameters of the main components of AR. Meanwhile, the regulatory effects and mechanisms of AR on DMEs and transporters are summarized to provide a theoretical and technical basis for the rational use of AR in clinical practice.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":" ","pages":"9-25"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846149","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

In silico ADME and target prediction studies of Alogliptin as drug molecule. 阿格列汀作为药物分子的ADME及靶标预测研究。

IF 3.4 2区医学

Drug Metabolism Reviews Pub Date : 2025-02-01 Epub Date: 2024-12-13 DOI: 10.1080/03602532.2024.2439102

Vaishnavi Sanjay Patil, Bhavika Kapil Seth, Hemchandra K Chaudhari

{"title":"In silico ADME and target prediction studies of Alogliptin as drug molecule.","authors":"Vaishnavi Sanjay Patil, Bhavika Kapil Seth, Hemchandra K Chaudhari","doi":"10.1080/03602532.2024.2439102","DOIUrl":"10.1080/03602532.2024.2439102","url":null,"abstract":"Alogliptin is an oral hypoglycemic agent selective inhibitor of the dipeptidyl peptidase-4 (DPP-4) enzyme. Inhibition of DPP-4 increases the levels of the incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) by preventing their degradation. The main goal is to study the predicted and experimental properties of absorption, distribution, metabolism, and elimination (ADME), compare them, examine predicted targets, and understand the use of SwissADME in designing other drug molecules. SwissADME, an online tool for ADME prediction, was used together with Swiss Target Prediction to understand drug targets. In addition, we obtained experimental data from the available scientific literature. Molecular docking studies against human DPP-4 were also conducted. We found similarities between the predicted and experimental data; however, some errors depended on the test conditions. The results are interpreted in the first half of the article. We describe the predicted ADME properties of Alogliptin, and based on the results, we can conclude that these tools can be used to predict other drug molecules similarly. It can also reconfigure and manufacture several different formulations of the drug based on predictive data.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":" ","pages":"1-8"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784480","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

Cytochrome P450-mediated carbon-carbon bond formation in drug metabolism. 细胞色素p450介导的碳-碳键在药物代谢中的形成。

IF 3.4 2区医学

Drug Metabolism Reviews Pub Date : 2025-02-01 Epub Date: 2025-02-05 DOI: 10.1080/03602532.2025.2451847

Joyce Liu, Donglu Zhang

引用次数: 0