Drug Metabolism Reviews最新文献_第9页

Pharmacokinetics, toxicological and clinical aspects of ulipristal acetate: insights into the mechanisms implicated in the hepatic toxicity. 醋酸乌普利司利的药代动力学，毒理学和临床方面:洞察涉及肝毒性的机制。

IF 5.9 2区医学

Drug Metabolism Reviews Pub Date : 2021-08-01 Epub Date: 2021-04-27 DOI: 10.1080/03602532.2021.1917599

Ricardo Jorge Dinis-Oliveira

{"title":"Pharmacokinetics, toxicological and clinical aspects of ulipristal acetate: insights into the mechanisms implicated in the hepatic toxicity.","authors":"Ricardo Jorge Dinis-Oliveira","doi":"10.1080/03602532.2021.1917599","DOIUrl":"https://doi.org/10.1080/03602532.2021.1917599","url":null,"abstract":"Ulipristal acetate is a drug used as emergency contraceptive (30 mg) and for the treatment of moderate to severe symptoms of uterine myomas (5 mg). After commercialization, and although the exact number is unknown, serious cases implying ulipristal acetate 5 mg as a contributing factor of liver injury, some leading to transplantation, were reported. These cases prompted to a restrict use of the drug in January 2021 by the European Medicines Agency. This work aimed to fully review pharmacokinetic aspects, namely focusing in the ulipristal acetate metabolism and other hypothetical toxicological underlying mechanisms that may predispose to drug-induced liver injury (DILI). The high lipophilicity, the extensive hepatic metabolism, the long half-life of the drug and of its major active metabolite, the long-term course of treatment, and possibility due to the formation of epoxide reactive may be contributing factors. Scientific results also points evidence to consider monitorization of liver function during ulipristal acetate treatment.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":"53 3","pages":"375-383"},"PeriodicalIF":5.9,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/03602532.2021.1917599","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38913390","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: 6

Novel advances in biotransformation and bioactivation research - 2020 year in review. 生物转化与生物活化研究新进展- 2020年回顾。

IF 5.9 2区医学

Drug Metabolism Reviews Pub Date : 2021-08-01 Epub Date: 2021-06-24 DOI: 10.1080/03602532.2021.1916028

S Cyrus Khojasteh, Upendra A Argikar, James P Driscoll, Carley J S Heck, Lloyd King, Klarissa D Jackson, Wenying Jian, Amit S Kalgutkar, Grover P Miller, Valerie Kramlinger, Ivonne M C M Rietjens, Aaron M Teitelbaum, Kai Wang, Cong Wei

引用次数: 4

Pharmacogenomics in the era of next generation sequencing - from byte to bedside. 下一代测序时代的药物基因组学——从字节到床边。

IF 5.9 2区医学

Drug Metabolism Reviews Pub Date : 2021-05-01 Epub Date: 2021-05-17 DOI: 10.1080/03602532.2021.1909613

Laura E Russell, Yitian Zhou, Ahmed A Almousa, Jasleen K Sodhi, Chukwunonso K Nwabufo, Volker M Lauschke

{"title":"Pharmacogenomics in the era of next generation sequencing - from byte to bedside.","authors":"Laura E Russell, Yitian Zhou, Ahmed A Almousa, Jasleen K Sodhi, Chukwunonso K Nwabufo, Volker M Lauschke","doi":"10.1080/03602532.2021.1909613","DOIUrl":"https://doi.org/10.1080/03602532.2021.1909613","url":null,"abstract":"Pharmacogenetic research has resulted in the identification of a multitude of genetic variants that impact drug response or toxicity. These polymorphisms are mostly common and have been included as actionable information in the labels of numerous drugs. In addition to common variants, recent advances in Next Generation Sequencing (NGS) technologies have resulted in the identification of a plethora of rare and population-specific pharmacogenetic variations with unclear functional consequences that are not accessible by conventional forward genetics strategies. In this review, we discuss how comprehensive sequencing information can be translated into personalized pharmacogenomic advice in the age of NGS. Specifically, we provide an update of the functional impacts of rare pharmacogenetic variability and how this information can be leveraged to improve pharmacogenetic guidance. Furthermore, we critically discuss the current status of implementation of pharmacogenetic testing across drug development and layers of care. We identify major gaps and provide perspectives on how these can be minimized to optimize the utilization of NGS data for personalized clinical decision-support.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":"53 2","pages":"253-278"},"PeriodicalIF":5.9,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/03602532.2021.1909613","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25562878","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: 16

Toxicogenomics of drug induced liver injury - from mechanistic understanding to early prediction. 药物性肝损伤的毒物基因组学——从机制理解到早期预测。

IF 5.9 2区医学

Drug Metabolism Reviews Pub Date : 2021-05-01 Epub Date: 2021-03-08 DOI: 10.1080/03602532.2021.1894571

Volker M Lauschke

{"title":"Toxicogenomics of drug induced liver injury - from mechanistic understanding to early prediction.","authors":"Volker M Lauschke","doi":"10.1080/03602532.2021.1894571","DOIUrl":"https://doi.org/10.1080/03602532.2021.1894571","url":null,"abstract":"Despite rigorous preclinical testing, clinical attrition rates in drug development remain high with drug-induced liver injury (DILI) remaining one of the most frequent causes of project failures. To understand DILI mechanisms, major efforts are put into the development of physiologically relevant cell models and culture paradigms with the aim to enhance preclinical to clinical result translation. While the majority of toxicogenomic studies have been based on cell lines, there are emerging trends toward the predominant use of stem cell-derived organoids and primary human hepatocytes in complex 3D cell models. Such studies have been successful in disentangling diverse toxicity mechanisms, including genotoxicity, mitochondrial injury, steatogenesis and cholestasis and can aid in distinguishing hepatotoxic from nontoxic structural analogs. Furthermore, by leveraging inter-individual differences of cells from different donors, these approaches can emulate the complexity of polygenic risk scores, which facilitates personalized drug-specific DILI risk analyses. In summary, toxicogenomic studies into drug-induced hepatotoxicity have majorly contributed to our mechanistic understanding of DILI and the incorporation of organotypic human 3D liver models into the preclinical testing arsenal promises to enhance biological insights during drug discovery, increase confidence in preclinical safety and minimize the translational gap.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":"53 2","pages":"245-252"},"PeriodicalIF":5.9,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/03602532.2021.1894571","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25459541","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: 11

International Society for the Study of Xenobiotics (ISSX) New Investigator Group Committee 2019-2020 concluding remarks. 国际异种生物研究学会(ISSX)新研究者小组委员会2019-2020结论性发言。

IF 5.9 2区医学

Drug Metabolism Reviews Pub Date : 2021-05-01 Epub Date: 2021-04-09 DOI: 10.1080/03602532.2021.1910293

Mary A Schleiff, Jasleen K Sodhi

引用次数: 1

Prediction of drug-induced kidney injury in drug discovery. 药物发现中药物性肾损伤的预测。

IF 5.9 2区医学

Drug Metabolism Reviews Pub Date : 2021-05-01 Epub Date: 2021-05-17 DOI: 10.1080/03602532.2021.1922436

Priyanka Kulkarni

{"title":"Prediction of drug-induced kidney injury in drug discovery.","authors":"Priyanka Kulkarni","doi":"10.1080/03602532.2021.1922436","DOIUrl":"https://doi.org/10.1080/03602532.2021.1922436","url":null,"abstract":"Drug induced kidney injury is one of the leading causes of failure of drug development programs in the clinic. Early prediction of renal toxicity potential of drugs is crucial to the success of drug candidates in the clinic. The dynamic nature of the functioning of the kidney and the presence of drug uptake proteins introduce additional challenges in the prediction of renal injury caused by drugs. Renal injury due to drugs can be caused by a wide variety of mechanisms and can be broadly classified as toxic or obstructive. Several biomarkers are available for in vitro and in vivo detection of renal injury. In vitro static and dynamic (microfluidic) cellular models and preclinical models can provide valuable information regarding the toxicity potential of drugs. Differences in pharmacology and subsequent disconnect in biomarker response, differences in the expression of transporter and enzyme proteins between in vitro to in vivo systems and between preclinical species and humans are some of the limitations of current experimental models. The progress in microfluidic (kidney-on-chip) platforms in combination with the ability of 3-dimensional cell culture can help in addressing some of these issues in the future. Finally, newer in silico and computational techniques like physiologically based pharmacokinetic modeling and machine learning have demonstrated potential in assisting prediction of drug induced kidney injury.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":"53 2","pages":"234-244"},"PeriodicalIF":5.9,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/03602532.2021.1922436","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38992147","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: 6

Introduction to the mini special issue on next generation drug discovery and development: rethinking translational pharmacology for accelerated drug development. 介绍新一代药物发现和开发的迷你特刊:重新思考加速药物开发的转化药理学。

IF 5.9 2区医学

Drug Metabolism Reviews Pub Date : 2021-05-01 Epub Date: 2021-05-07 DOI: 10.1080/03602532.2021.1909614

Chukwunonso K Nwabufo

{"title":"Introduction to the mini special issue on next generation drug discovery and development: rethinking translational pharmacology for accelerated drug development.","authors":"Chukwunonso K Nwabufo","doi":"10.1080/03602532.2021.1909614","DOIUrl":"https://doi.org/10.1080/03602532.2021.1909614","url":null,"abstract":"The coronavirus disease (COVID-19) pandemic further revealed the barriers to accelerated discovery and development of transformative medicines for life threatening diseases. To effectively and efficiently respond to unmet medical needs, efforts should be directed towards revolutionizing the predictive capability of non-clinical surrogates that inform drug discovery and development programs. I developed this mini special issue amidst the COVID-19 pandemic to evaluate recent advancements and opportunities for four main subthemes that support drug discovery and development including prediction of metabolic pathways, translational pharmacokinetic and pharmacodynamic studies, pharmacogenomics, and trends in bioanalysis. Scientific papers in these areas were covered by investigators from the International Society for the Study of Xenobiotics New Investigator Group and other investigators. Advancement in the predictive capability of in silico, in vitro, and in vivo models used to determine the absorption, distribution, metabolism, excretion, and toxicity profile of investigational drugs can help offset the cost of unexpected safety and/or efficacy issues during clinical studies. Likewise, extensive application of pharmacogenomics in drug development and clinical care can help direct therapeutic benefits to the appropriate patient population with the overall goal of accelerating drug development and mitigating failed drug cost. Finally, I hope that the scientific contributions in this mini special issue will stimulate practical advancements across all aspects of basic science research that support drug discovery and development to help unlock the door to the next generation of drug discovery and development that features reduced failure rates and accelerated development.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":"53 2","pages":"171-172"},"PeriodicalIF":5.9,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/03602532.2021.1909614","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38960858","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: 4

Recent developments in predicting CYP-independent metabolism. 预测cypp非依赖性代谢的最新进展。

IF 5.9 2区医学

Drug Metabolism Reviews Pub Date : 2021-05-01 Epub Date: 2021-05-25 DOI: 10.1080/03602532.2021.1923728

Nikhilesh V Dhuria, Bianka Haro, Amit Kapadia, Khadjia A Lobo, Bernice Matusow, Mary A Schleiff, Christina Tantoy, Jasleen K Sodhi

引用次数: 4

Recent developments in in vitro and in vivo models for improved translation of preclinical pharmacokinetics and pharmacodynamics data. 体外和体内模型的最新进展，以改善临床前药代动力学和药效学数据的翻译。

IF 5.9 2区医学

Drug Metabolism Reviews Pub Date : 2021-05-01 Epub Date: 2021-05-25 DOI: 10.1080/03602532.2021.1922435

Jaydeep Yadav, Mehdi El Hassani, Jasleen Sodhi, Volker M Lauschke, Jessica H Hartman, Laura E Russell

引用次数: 11

Recent advances in computational metabolite structure predictions and altered metabolic pathways assessment to inform drug development processes. 计算代谢物结构预测和改变代谢途径评估的最新进展，为药物开发过程提供信息。

IF 5.9 2区医学

Drug Metabolism Reviews Pub Date : 2021-05-01 Epub Date: 2021-05-11 DOI: 10.1080/03602532.2021.1910292

Mary Alexandra Schleiff, Deepika Dhaware, Jasleen K Sodhi

{"title":"Recent advances in computational metabolite structure predictions and altered metabolic pathways assessment to inform drug development processes.","authors":"Mary Alexandra Schleiff, Deepika Dhaware, Jasleen K Sodhi","doi":"10.1080/03602532.2021.1910292","DOIUrl":"https://doi.org/10.1080/03602532.2021.1910292","url":null,"abstract":"Many drug candidates fail during preclinical and clinical trials due to variable or unexpected metabolism which may lead to variability in drug efficacy or adverse drug reactions. The drug metabolism field aims to address this important issue from many angles which range from the study of drug-drug interactions, pharmacogenomics, computational metabolic modeling, and others. This manuscript aims to provide brief but comprehensive manuscript summaries highlighting the conclusions and scientific importance of seven exceptional manuscripts published in recent years within the field of drug metabolism. Two main topics within the field are reviewed: novel computational metabolic modeling approaches which provide complex outputs beyond site of metabolism predictions, and experimental approaches designed to discern the impacts of interindividual variability and species differences on drug metabolism. The computational approaches discussed provide novel outputs in metabolite structure and formation likelihood and/or extend beyond the saturated field of drug phase I metabolism, while the experimental metabolic pathways assessments aim to highlight the impacts of genetic polymorphisms and clinical animal model metabolic differences on human metabolism and subsequent health outcomes.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":"53 2","pages":"173-187"},"PeriodicalIF":5.9,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/03602532.2021.1910292","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25581116","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: 2