In vitro and in vivo testing in animals have not always predicted human drug metabolism. The present study investigated whether chimeric mice could provide a more predictive assessment of the clinical metabolism of clemizole, a drug in clinical development for hepatitis C virus (HCV) infection. The results demonstrated that pharmacokinetics performed in chimeric mice correctly identified the predominant human drug metabolite. The differences in the rodent and human pathways for clemizole metabolism were of importance because the predominant human metabolite had anti-HCV activity. In addition, studies in chimeric mice correctly predicted that a drug-drug interaction would occur when administered with a CYP3A4 inhibitor.
See article at J Pharmacol Exp Ther 2013, 344:388–396.
- Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics