Drug Metabolism Reviews最新文献_第8页

Mechanisms of intestinal pharmacokinetic natural product-drug interactions. 肠道药代动力学天然产品与药物相互作用的机制。

IF 3.8 2区医学

Drug Metabolism Reviews Pub Date : 2024-08-01 Epub Date: 2024-08-12 DOI: 10.1080/03602532.2024.2386597

Victoria O Oyanna, John D Clarke

{"title":"Mechanisms of intestinal pharmacokinetic natural product-drug interactions.","authors":"Victoria O Oyanna, John D Clarke","doi":"10.1080/03602532.2024.2386597","DOIUrl":"10.1080/03602532.2024.2386597","url":null,"abstract":"The growing co-consumption of botanical natural products with conventional medications has intensified the need to understand potential effects on drug safety and efficacy. This review delves into the intricacies of intestinal pharmacokinetic interactions between botanical natural products and drugs, such as alterations in drug solubility, permeability, transporter activity, and enzyme-mediated metabolism. It emphasizes the importance of understanding how drug solubility, dissolution, and osmolality interplay with botanical constituents in the gastrointestinal tract, potentially altering drug absorption and systemic exposure. Unlike reviews that focus primarily on enzyme and transporter mechanisms, this article highlights the lesser known but equally important mechanisms of interaction. Applying the Biopharmaceutics Drug Disposition Classification System (BDDCS) can serve as a framework for predicting and understanding these interactions. Through a comprehensive examination of specific botanical natural products such as byakkokaninjinto, green tea catechins, goldenseal, spinach extract, and quercetin, we illustrate the diversity of these interactions and their dependence on the physicochemical properties of the drug and the botanical constituents involved. This understanding is vital for healthcare professionals to effectively anticipate and manage potential natural product-drug interactions, ensuring optimal patient therapeutic outcomes. By exploring these emerging mechanisms, we aim to broaden the scope of natural product-drug interaction research and encourage comprehensive studies to better elucidate complex mechanisms.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":" ","pages":"285-301"},"PeriodicalIF":3.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11606768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Metabolism of new drug modalities research advances - 2023 year in review. 新药代谢研究进展 - 2023 年回顾。

IF 3.8 2区医学

Drug Metabolism Reviews Pub Date : 2024-08-01 Epub Date: 2024-07-05 DOI: 10.1080/03602532.2024.2370331

Bin Ma, Upendra A Argikar, Lionel Cheruzel, Sungjoon Cho, Simon Hauri, Kevin M Johnson, Joyce Liu, Simone Schadt, Shuai Wang, S Cyrus Khojasteh

引用次数: 0

Biotransformation Research Advances – 2023 year in review 生物转化研究进展 - 2023 年回顾

IF 5.9 2区医学

Drug Metabolism Reviews Pub Date : 2024-06-19 DOI: 10.1080/03602532.2024.2370330

S.Cyrus Khojasteh, UpendraA Argikar, Maria Chatzopoulou, Lionel Cheruzel, Sungjoon Cho, Deepika Dhaware, KevinM Johnson, AmitS Kalgutkar, Joyce Liu, Bin Ma, Hlaing Maw, JessicaA Rowley, HeranaKamal Seneviratne, Shuai Wang

引用次数: 0

The potential impact of CYP and UGT drug-metabolizing enzymes on brain target site drug exposure. CYP 和 UGT 药物代谢酶对大脑靶点药物暴露的潜在影响。

IF 3.8 2区医学

Drug Metabolism Reviews Pub Date : 2024-02-01 Epub Date: 2024-01-10 DOI: 10.1080/03602532.2023.2297154

Mengxu Zhang, Vivi Rottschäfer, Elizabeth C M de Lange

{"title":"The potential impact of CYP and UGT drug-metabolizing enzymes on brain target site drug exposure.","authors":"Mengxu Zhang, Vivi Rottschäfer, Elizabeth C M de Lange","doi":"10.1080/03602532.2023.2297154","DOIUrl":"10.1080/03602532.2023.2297154","url":null,"abstract":"Drug metabolism is one of the critical determinants of drug disposition throughout the body. While traditionally associated with the liver, recent research has unveiled the presence and functional significance of drug-metabolizing enzymes (DMEs) within the brain. Specifically, cytochrome P-450 enzymes (CYPs) and UDP-glucuronosyltransferases (UGTs) enzymes have emerged as key players in drug biotransformation within the central nervous system (CNS). This comprehensive review explores the cellular and subcellular distribution of CYPs and UGTs within the CNS, emphasizing regional expression and contrasting profiles between the liver and brain, humans and rats. Moreover, we discuss the impact of species and sex differences on CYPs and UGTs within the CNS. This review also provides an overview of methodologies for identifying and quantifying enzyme activities in the brain. Additionally, we present factors influencing CYPs and UGTs activities in the brain, including genetic polymorphisms, physiological variables, pathophysiological conditions, and environmental factors. Examples of CYP- and UGT-mediated drug metabolism within the brain are presented at the end, illustrating the pivotal role of these enzymes in drug therapy and potential toxicity. In conclusion, this review enhances our understanding of drug metabolism's significance in the brain, with a specific focus on CYPs and UGTs. Insights into the expression, activity, and influential factors of these enzymes within the CNS have crucial implications for drug development, the design of safe drug treatment strategies, and the comprehension of drug actions within the CNS. To that end, CNS pharmacokinetic (PK) models can be improved to further advance drug development and personalized therapy.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":" ","pages":"1-30"},"PeriodicalIF":3.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138828752","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

Investigating the association between CYP2J2 inhibitors and QT prolongation: a literature review. 研究 CYP2J2 抑制剂与 QT 延长之间的关系：文献综述。

IF 3.8 2区医学

Drug Metabolism Reviews Pub Date : 2024-02-01 Epub Date: 2024-03-20 DOI: 10.1080/03602532.2024.2329928

Alexandra M Wiley, Jade Yang, Rivcka Madhani, Abhinav Nath, Rheem A Totah

{"title":"Investigating the association between CYP2J2 inhibitors and QT prolongation: a literature review.","authors":"Alexandra M Wiley, Jade Yang, Rivcka Madhani, Abhinav Nath, Rheem A Totah","doi":"10.1080/03602532.2024.2329928","DOIUrl":"10.1080/03602532.2024.2329928","url":null,"abstract":"Drug withdrawal post-marketing due to cardiotoxicity is a major concern for drug developers, regulatory agencies, and patients. One common mechanism of cardiotoxicity is through inhibition of cardiac ion channels, leading to prolongation of the QT interval and sometimes fatal arrythmias. Recently, oxylipin signaling compounds have been shown to bind to and alter ion channel function, and disruption in their cardiac levels may contribute to QT prolongation. Cytochrome P450 2J2 (CYP2J2) is the predominant CYP isoform expressed in cardiomyocytes, where it oxidizes arachidonic acid to cardioprotective epoxyeicosatrienoic acids (EETs). In addition to roles in vasodilation and angiogenesis, EETs bind to and activate various ion channels. CYP2J2 inhibition can lower EET levels and decrease their ability to preserve cardiac rhythm. In this review, we investigated the ability of known CYP inhibitors to cause QT prolongation using Certara's Drug Interaction Database. We discovered that among the multiple CYP isozymes, CYP2J2 inhibitors were more likely to also be QT-prolonging drugs (by approximately 2-fold). We explored potential binding interactions between these inhibitors and CYP2J2 using molecular docking and identified four amino acid residues (Phe61, Ala223, Asn231, and Leu402) predicted to interact with QT-prolonging drugs. The four residues are located near the opening of egress channel 2, highlighting the potential importance of this channel in CYP2J2 binding and inhibition. These findings suggest that if a drug inhibits CYP2J2 and interacts with one of these four residues, then it may have a higher risk of QT prolongation and more preclinical studies are warranted to assess cardiovascular safety.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":" ","pages":"145-163"},"PeriodicalIF":3.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140119108","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

Biopolymers as promising vehicles for drug delivery to the brain. 生物聚合物作为药物输送到大脑的有前途的载体。

IF 3.8 2区医学

Drug Metabolism Reviews Pub Date : 2024-02-01 Epub Date: 2023-11-14 DOI: 10.1080/03602532.2023.2281855

Rajeswara Babu Mythri, Mysore Rajeswara Babu Aishwarya

{"title":"Biopolymers as promising vehicles for drug delivery to the brain.","authors":"Rajeswara Babu Mythri, Mysore Rajeswara Babu Aishwarya","doi":"10.1080/03602532.2023.2281855","DOIUrl":"10.1080/03602532.2023.2281855","url":null,"abstract":"The brain is a privileged organ, tightly guarded by a network of endothelial cells, pericytes, and glial cells called the blood brain barrier. This barrier facilitates tight regulation of the transport of molecules, ions, and cells from the blood to the brain. While this feature ensures protection to the brain, it also presents a challenge for drug delivery for brain diseases. It is, therefore, crucial to identify molecules and/or vehicles that carry drugs, cross the blood brain barrier, and reach targets within the central nervous system. Biopolymers are large polymeric molecules obtained from biological sources. In comparison with synthetic polymers, biopolymers are structurally more complex and their 3D architecture makes them biologically active. Researchers are therefore investigating biopolymers as safe and efficient carriers of brain-targeted therapeutic agents. In this article, we bring together various approaches toward achieving this objective with a note on the prospects for biopolymer-based neurotherapeutic/neurorestorative/neuroprotective interventions. Finally, as a representative paradigm, we discuss the potential use of nanocarrier biopolymers in targeting protein aggregation diseases.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":" ","pages":"46-61"},"PeriodicalIF":3.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89717350","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

Metabolic bioactivation of antidepressants: advance and underlying hepatotoxicity. 抗抑郁药的代谢生物活化：进展和潜在的肝毒性。

IF 3.8 2区医学

Drug Metabolism Reviews Pub Date : 2024-02-01 Epub Date: 2024-02-20 DOI: 10.1080/03602532.2024.2313967

Saleh M Khalil, Kevin R MacKenzie, Mirjana Maletic-Savatic, Feng Li

{"title":"Metabolic bioactivation of antidepressants: advance and underlying hepatotoxicity.","authors":"Saleh M Khalil, Kevin R MacKenzie, Mirjana Maletic-Savatic, Feng Li","doi":"10.1080/03602532.2024.2313967","DOIUrl":"10.1080/03602532.2024.2313967","url":null,"abstract":"Many drugs that serve as first-line medications for the treatment of depression are associated with severe side effects, including liver injury. Of the 34 antidepressants discussed in this review, four have been withdrawn from the market due to severe hepatotoxicity, and others carry boxed warnings for idiosyncratic liver toxicity. The clinical and economic implications of antidepressant-induced liver injury are substantial, but the underlying mechanisms remain elusive. Drug-induced liver injury may involve the host immune system, the parent drug, or its metabolites, and reactive drug metabolites are one of the most commonly referenced risk factors. Although the precise mechanism by which toxicity is induced may be difficult to determine, identifying reactive metabolites that cause toxicity can offer valuable insights for decreasing the bioactivation potential of candidates during the drug discovery process. A comprehensive understanding of drug metabolic pathways can mitigate adverse drug-drug interactions that may be caused by elevated formation of reactive metabolites. This review provides a comprehensive overview of the current state of knowledge on antidepressant bioactivation, the metabolizing enzymes responsible for the formation of reactive metabolites, and their potential implication in hepatotoxicity. This information can be a valuable resource for medicinal chemists, toxicologists, and clinicians engaged in the fields of antidepressant development, toxicity, and depression treatment.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":" ","pages":"97-126"},"PeriodicalIF":3.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11118075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139680889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Melatonin in cancer biology: pathways, derivatives, and the promise of targeted delivery. 癌症生物学中的褪黑激素：癌症生物学中的褪黑激素：途径、衍生物和靶向给药的前景》（Pathways, Derivatives, and the Promise of Targeted Delivery）。

IF 3.8 2区医学

Drug Metabolism Reviews Pub Date : 2024-02-01 Epub Date: 2024-01-30 DOI: 10.1080/03602532.2024.2305764

Yu-Juan Yi, Hong Tang, Peng-Lai Pi, Han-Wen Zhang, Si-Yu Du, Wei-Ye Ge, Qi Dai, Zi-Yan Zhao, Jia Li, Zheng Sun

{"title":"Melatonin in cancer biology: pathways, derivatives, and the promise of targeted delivery.","authors":"Yu-Juan Yi, Hong Tang, Peng-Lai Pi, Han-Wen Zhang, Si-Yu Du, Wei-Ye Ge, Qi Dai, Zi-Yan Zhao, Jia Li, Zheng Sun","doi":"10.1080/03602532.2024.2305764","DOIUrl":"10.1080/03602532.2024.2305764","url":null,"abstract":"Melatonin, historically recognized for its primary role in regulating circadian rhythms, has expanded its influence particularly due to its wide range of biological activities. It has firmly established itself in cancer research. To highlight its versatility, we delved into how melatonin interacts with key signaling pathways, such as the Wnt/β-Catenin, PI3K, and NF-κB pathways, which play foundational roles in tumor development and progression. Notably, melatonin can intricately modulate these pathways, potentially affecting various cellular functions such as apoptosis, metastasis, and immunity. Additionally, a comprehensive review of current clinical studies provides a dual perspective. These studies confirm melatonin's potential in cancer management but also underscore its inherent limitations, particularly its limited bioavailability, which often relegates it to a supplementary role in treatments. Despite this limitation, there is an ongoing quest for innovative solutions and current advancements include the development of melatonin derivatives and cutting-edge delivery systems. By synthesizing the past, present, and future, this review provides a detailed overview of melatonin's evolving role in oncology, positioning it as a potential cornerstone in future cancer therapeutics.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":" ","pages":"62-79"},"PeriodicalIF":3.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139471383","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

The aminosalicylate - folate connection. 氨基水杨酸盐与叶酸的联系。

IF 3.8 2区医学

Drug Metabolism Reviews Pub Date : 2024-02-01 Epub Date: 2024-01-17 DOI: 10.1080/03602532.2024.2303507

Robert E London

{"title":"The aminosalicylate - folate connection.","authors":"Robert E London","doi":"10.1080/03602532.2024.2303507","DOIUrl":"10.1080/03602532.2024.2303507","url":null,"abstract":"Two aminosalicylate isomers have been found to possess useful pharmacological behavior: p-aminosalicylate (PAS, 4AS) is an anti-tubercular agent that targets M. tuberculosis, and 5-aminosalicylate (5AS, mesalamine, mesalazine) is used in the treatment of ulcerative colitis (UC) and other inflammatory bowel diseases (IBD). PAS, a structural analog of pABA, is biosynthetically incorporated by bacterial dihydropteroate synthase (DHPS), ultimately yielding a dihydrofolate (DHF) analog containing an additional hydroxyl group in the pABA ring: 2'-hydroxy-7,8-dihydrofolate. It has been reported to perturb folate metabolism in M. tuberculosis, and to selectively target M. tuberculosis dihydrofolate reductase (mtDHFR). Studies of PAS metabolism are reviewed, and possible mechanisms for its mtDHFR inhibition are considered. Although 5AS is a more distant structural relative of pABA, multiple lines of evidence suggest a related role as a pABA antagonist that inhibits bacterial folate biosynthesis. Structural data support the likelihood that 5AS is recognized by the DHPS pABA binding site, and its effects probably range from blocking pABA binding to formation of a dead-end dihydropterin-5AS adduct. These studies suggest that mesalamine acts as a gut bacteria-directed antifolate, that selectively targets faster growing, more folate-dependent species.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":" ","pages":"80-96"},"PeriodicalIF":3.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11305456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139478213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Favipiravir, remdesivir, and lopinavir: metabolites, degradation products and their analytical methods. 法维拉韦、雷米替韦和洛匹那韦：代谢物、降解产物及其分析方法。

IF 3.8 2区医学

Drug Metabolism Reviews Pub Date : 2024-02-01 Epub Date: 2024-03-06 DOI: 10.1080/03602532.2024.2326415

Mir Saleh Hoseininezhad-Namin, Elaheh Rahimpour, Abolghasem Jouyban

{"title":"Favipiravir, remdesivir, and lopinavir: metabolites, degradation products and their analytical methods.","authors":"Mir Saleh Hoseininezhad-Namin, Elaheh Rahimpour, Abolghasem Jouyban","doi":"10.1080/03602532.2024.2326415","DOIUrl":"10.1080/03602532.2024.2326415","url":null,"abstract":"Severe acute respiratory syndrome 2 (SARS-CoV-2) caused the emergence of the COVID-19 pandemic all over the world. Several studies have suggested that antiviral drugs such as favipiravir (FAV), remdesivir (RDV), and lopinavir (LPV) may potentially prevent the spread of the virus in the host cells and person-to-person transmission. Simultaneously with the widespread use of these drugs, their stability and action mechanism studies have also attracted the attention of many researchers. This review focuses on the action mechanism, metabolites and degradation products of these antiviral drugs (FAV, RDV and LPV) and demonstrates various methods for their quantification and discrimination in the different biological samples. Herein, the instrumental methods for analysis of the main form of drugs or their metabolite and degradation products are classified into two types: optical and chromatography methods which the last one in combination with various detectors provides a powerful method for routine and stability analyses. Some representative studies are reported in this review and the details of them are carefully explained. It is hoped that this review will be a good guideline study and provide a better understanding of these drugs from the aspects investigated in this study.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":" ","pages":"127-144"},"PeriodicalIF":3.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140038944","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