Drug-Induced Liver Injury (DILI): Mechanisms and Mitigation

This lecture explores Drug-Induced Liver Injury (DILI), a major concern in drug development, discussing the two types of DILI, intrinsic and idiosyncratic, and the role of liver metabolism. It covers the formation of reactive metabolites, the impact of cytochrome P450 enzymes, and the importance of Phase II detoxification pathways. The session also delves into the mitigation strategies for P450-induced reactive metabolite formation, emphasizing the significance of Structure-Metabolism Relationship (SMR) studies. Additionally, it addresses the challenges associated with acyl-glucuronide formation and the potential risks of drug bioactivation. The lecture concludes with a discussion on the critical role of mechanistic biochemistry in drug discovery, highlighting the importance of understanding perplexing data for innovative drug development.