Drug Metabolism in Preclinical Drug Development: A Survey of the Discovery Process Toxicology and Computational Tools

摘要

Increased R & D spending and high failure rates exist in drug development, due in part to inadequate prediction of drug metabolism and its consequences in the human body. Hence, there is a need for computational methods to supplement and complement current biological assessment strategies. In this review, we provide an overview of drug metabolism in pharmacology, and discuss the current in vitro and in vivo strategies for assessing drug metabolism in preclinical drug development. We highlight computational tools available to the scientific community for the in silico prediction of drug metabolism, and examine how these tools have been implemented to produce drug-target signatures relevant to metabolic routes. Computational workflows that assess drug metabolism and its toxicological and pharmacokinetic effects, such as by applying the adverse outcome pathway framework for risk assessment, may improve the efficiency and speed of preclinical drug development.