Role of biotransformation in drug-induced toxicity: influence of intra- and inter-species differences in drug metabolism.
Role of biotransformation in drug-induced toxicity: influence of intra- and inter-species differences in drug metabolism.
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DOI：
10.2133/dmpk.dmpk-10-rv-089
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发表时间：
2011
影响因子：
2.1
通讯作者：
Rettie AE
中科院分区：
文献类型：
--
作者：
Baillie TA;Rettie AE
现在人们普遍认识到，除了母体药物本身之外，药物代谢物还可以介导新治疗药物的严重不良反应，因此学术界、制药行业和监管机构的研究人员对药物代谢领域的兴趣日益浓厚。近年来，在了解药物代谢物引起的毒性机制以及影响个体接触药物生物转化产物的众多因素方面取得了很大进展。本综述讨论了其中一些因素，包括药物间相互作用的作用、反应性代谢物的形成、个体易感性以及药物代谢酶遗传多态性引起的药物处置的物种差异。提供了与药物代谢相关的不良反应的例子，并讨论了毒性反应变异性的潜在机制。最后，在发现和开发新治疗剂的背景下，强调了该领域的一些未来研究方向。
It is now widely appreciated that drug metabolites, in addition to the parent drugs themselves, can mediate the serious adverse effects of new therapeutic agents, as a result of which there has been heightened interest in the field of drug metabolism from researchers in academia, the pharmaceutical industry, and regulatory agencies. Much progress has been made in recent years in understanding mechanisms of toxicities caused by drug metabolites, and the numerous factors that influence individual exposure to products of drug biotransformation. This review addresses some of these factors, including the role of drug-drug interactions, reactive metabolite formation, individual susceptibility, and species differences in drug disposition caused by genetic polymorphisms in drug metabolizing enzymes. Examples are provided of adverse reactions that are linked to drug metabolism, and the mechanisms underlying variability in toxic response are discussed. Finally, some future directions for research in this field are highlighted in the context of the discovery and development of new therapeutic agents.