Application of systems pharmacology to explore mechanisms of hepatotoxicity.

Advances in systems biology have allowed the development of a highly characterized systems pharmacology model to study mechanisms of drug-induced hepatotoxicity. In this issue of CPT, Yang et al. describe a model, DILIsym, used to characterize mechanisms of hepatotoxicity of troglitazone. Their modeling approach has provided new insight into troglitazone-induced hepatotoxicity in humans but is not associated with hepatotoxicity in rats, consistent with preclinical data for this drug.