Chapter 12: Predicting Drug-Induced Mitochondrial Dysfunction

Drug-induced mitochondrial dysfunction is a contributor to both late-stage compound attrition and post-market drug withdrawals. As a result, mitochondrial toxicity testing is gradually being recognized by pharmaceutical companies and contract research organizations as an essential part of toxicity testing that needs to be implemented early in the drug discovery process. This chapter provides an overview on mitochondrial physiology, the mechanisms which lead to drug-induced mitochondrial dysfunction, high-throughput in vitro assays which are currently being used to predict drug-induced mitochondrial dysfunction, and the drugs which have been identified by in vitro assays as contributors to mitochondrial toxicity. The chapter concludes with a discussion on the challenges of predicting drug-induced mitochondrial dysfunction such as the development of in silico models, wider acceptance of using suitable animal models, identification and validation of relevant biomarkers, and the translation of in vitro/in vivo results to clinical outcomes.