Evaluation of DILI Predictive Hypotheses in Early Drug Development.

ABSTRACT: Drug-induced liver injury (DILI) is a leading cause of drug failure in clinical trials and a major reason for drug withdrawals. DILI has been shown to be dependent on both daily dose and extent of hepatic metabolism. Yet, early in drug development daily dose is unknown. Here, we perform a comprehensive analysis of the published hypotheses that attempt to predict DILI, including a new analysis of the Biopharmaceutics Drug Disposition Classification System (BDDCS) in evaluating the severity of DILI warnings in drug labels approved by the FDA and the withdrawal status due to adverse drug reactions (ADRs). Our analysis confirms that higher doses ≥50 mg/day lead to increased DILI potential, but this property alone is not sufficient to predict the DILI potential. We evaluate prior attempts to ca

SUBMITTER: Chan R 

PROVIDER: S-EPMC5674994 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature