Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Zürich, 8093 Zürich, Switzerland; and the Center for Bioinformatics, University of Hamburg, 20146 Hamburg, Germany.
Global Drug Discovery, Bayer Pharma AG, 42096 Wuppertal, Germany.
Nat Rev Drug Discov. 2015 Jun;14(6):387-404. doi: 10.1038/nrd4581. Epub 2015 Apr 24.
Drug metabolism can produce metabolites with physicochemical and pharmacological properties that differ substantially from those of the parent drug, and consequently has important implications for both drug safety and efficacy. To reduce the risk of costly clinical-stage attrition due to the metabolic characteristics of drug candidates, there is a need for efficient and reliable ways to predict drug metabolism in vitro, in silico and in vivo. In this Perspective, we provide an overview of the state of the art of experimental and computational approaches for investigating drug metabolism. We highlight the scope and limitations of these methods, and indicate strategies to harvest the synergies that result from combining measurement and prediction of drug metabolism.
药物代谢可以产生具有显著不同于母体药物的理化性质和药理学性质的代谢物，因此对药物的安全性和疗效都有重要影响。为了降低由于候选药物的代谢特征而导致在临床阶段淘汰的风险，需要有效的、可靠的方法来预测体外、体内和体内的药物代谢。在本观点中，我们提供了一种用于研究药物代谢的实验和计算方法的最新概述。我们强调了这些方法的范围和局限性，并指出了从药物代谢的测量和预测相结合中获取协同作用的策略。
