Drug Metabolism Reviews最新文献_第2页

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 3.4 2区医学

Drug Metabolism Reviews Pub 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":"https://doi.org/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":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-05","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

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

Ocular Drug-Metabolizing Enzymes: Focus on Esterases. 眼部药物代谢酶：聚焦酯酶。

IF 5.9 2区医学

Drug Metabolism Reviews Pub Date : 2024-06-18 DOI: 10.1080/03602532.2024.2368247

Anam Hammid, Paavo Honkakoski

引用次数: 0

Advances in drug resistance of osteosarcoma caused by pregnane X receptor. 孕烷 X 受体导致骨肉瘤耐药性的研究进展。

IF 5.9 2区医学

Drug Metabolism Reviews Pub Date : 2024-06-13 DOI: 10.1080/03602532.2024.2366948

Kunhong Mao, Can Liu, Zhongwen Tang, Zhouzhou Rao, Jie Wen

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 5.9 2区医学

Drug Metabolism Reviews Pub 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":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-05-03","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

Effects of Cannabidiol and Δ9-Tetrahydrocannabinol on Cytochrome P450 Enzymes: A Systematic Review. 大麻二酚和Δ9-四氢大麻酚对细胞色素 P450 酶的影响：系统综述。

IF 5.9 2区医学

Drug Metabolism Reviews Pub Date : 2024-04-24 DOI: 10.1080/03602532.2024.2346767

Sarah Ann Smith, Gia Han Le, K. Teopiz, A. Kwan, T. Rhee, Roger C. Ho, Jie Wu, Bing Cao, Felicia Ceban, R. McIntyre

{"title":"Effects of Cannabidiol and Δ9-Tetrahydrocannabinol on Cytochrome P450 Enzymes: A Systematic Review.","authors":"Sarah Ann Smith, Gia Han Le, K. Teopiz, A. Kwan, T. Rhee, Roger C. Ho, Jie Wu, Bing Cao, Felicia Ceban, R. McIntyre","doi":"10.1080/03602532.2024.2346767","DOIUrl":"https://doi.org/10.1080/03602532.2024.2346767","url":null,"abstract":"Due to legal, political, and cultural changes, the use of cannabis has rapidly increased in recent years. Research has demonstrated that the cannabinoids cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) inhibit and induce cytochrome P450 (CYP450) enzymes. The objective of this review is to evaluate the effect of CBD and THC on the activity of CYP450 enzymes and the implications for drug-drug interactions (DDIs) with psychotropic agents that are CYP substrates. A systematic search was conducted using PubMed, Scopus, Scientific Electronic Library Online (SciELO) and PsychINFO. Search terms included 'cannabidiol', 'tetrahydrocannabinol and 'cytochrome P450'. A total of seven studies evaluating the interaction of THC and CBD with CYP450 enzymes and psychotropic drugs were included. Both preclinical and clinical studies were included.Results from the included studies indicate that both CBD and THC inhibit several CYP450 enzymes including, but not limited to, CYP1A2, CYP3C19, and CYP2B6. While there are a few known CYP450 enzymes that are induced by THC and CBD, the induction of CYP450 enzymes is an understudied area of research and lacks clinical data. The inhibitory effects observed by CBD and THC on CYP450 enzymes vary in magnitude and may decrease the metabolism of psychotropic agents, changes in plasma levels of psychotropic medications, and increase adverse effects. Our findings clearly present interactions between THC and CBD and several CYP450 enzymes, providing clinicians evidence of a high risk of DDIs for patients who consume both cannabis and psychotropic medication. However, more clinical research is necessary before results are applied to clinical settings.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140661775","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 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 5.9 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":null,"pages":null},"PeriodicalIF":5.9,"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 5.9 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":null,"pages":null},"PeriodicalIF":5.9,"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 5.9 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":null,"pages":null},"PeriodicalIF":5.9,"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 5.9 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":null,"pages":null},"PeriodicalIF":5.9,"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