Minimizing the Potential for Drug Bioactivation of Drug Candidates to Success in Clinical Development

Abstract Variations in human drug‐metabolizing enzymes can produce subtle evidence of potential toxicity. There are indications that some substructures found in drugs can form reactive metabolites that are involved in toxicities in humans. This article discusses the recent efforts to overcome and assess the problem of reactive metabolites in drug discovery and development, which might help to evaluate the safety profile of new drug candidates for idiosyncratic drug reactions (IDRs) during the preclinical phase.