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”].

中文翻译：

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个体人细胞色素 P450 酶在药物代谢中的作用


在过去的 30 年中，我们对单个细胞色素 P450 （P450） 酶在药物代谢中的作用的了解有了长足的发展，这个基础在避免药物相互作用的严重问题和由于变异引起的问题方面具有相当大的用途。正在考虑使用新的候选药物对代谢反应进行“表型分析”的新方法。内源性生物标志物用于无创估计单个 P450 酶的水平。还有一些剩余的“孤儿”P450 的问题，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相互作用、预测多态性和其他 P450 变异的影响以及评估药物代谢的种间差异，特别是在“安全性测试中的代谢”监管问题 [“不成比例的（人类）代谢物”] 的背景下。