Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee
Pharmacol Rev. 2024 Oct 16;76(6):1104-1132. doi: 10.1124/pharmrev.124.001173.
Our knowledge of the roles of individual cytochrome P450 (P450) enzymes in drug metabolism has developed considerably in the past 30 years, and this base has been of considerable use in avoiding serious issues with drug interactions and issues due to variations. Some newer approaches are being considered for "phenotyping" metabolism reactions with new drug candidates. Endogenous biomarkers are being used for noninvasive estimation of levels of individual P450 enzymes. There is also the matter of some remaining "orphan" P450s, which have yet to be assigned reactions. Practical problems that continue in drug development include predicting drug-drug interactions, predicting the effects of polymorphic and other P450 variations, and evaluating interspecies differences in drug metabolism, particularly in the context of "metabolism in safety testing" regulatory issues ["disproportionate (human) metabolites"]. SIGNIFICANCE STATEMENT: Cytochrome P450 enzymes are the major catalysts involved in drug metabolism. The characterization of their individual roles has major implications in drug development and clinical practice.
在过去的 30 年中，我们对细胞色素 P450（P450）酶在药物代谢中的作用的了解有了相当大的发展，这一基础在避免药物相互作用和因变异而产生的问题方面非常有用。一些新的方法正在考虑用于对新药物候选物的代谢反应进行“表型分析”。内源性生物标志物正被用于非侵入性地估计个体 P450 酶的水平。还有一些剩余的“孤儿”P450，它们尚未被分配反应。药物开发中持续存在的实际问题包括预测药物-药物相互作用、预测多态性和其他 P450 变异的影响，以及评估种间药物代谢差异，特别是在“安全测试中的代谢”监管问题[“不成比例的（人体）代谢物”]的背景下。
细胞色素 P450 酶是参与药物代谢的主要催化剂。它们各自作用的特征在药物开发和临床实践中具有重大意义。
