The Utility of in Vitro Cytochrome P450 Inhibition Data in the Prediction of Drug-Drug Interactions

  title={The Utility of in Vitro Cytochrome P450 Inhibition Data in the Prediction of Drug-Drug Interactions},
  author={R. Scott Obach and Robert L. Walsky and Karthik Venkatakrishnan and Emily A. Gaman and J. Brian Houston and Larry M. Tremaine},
  journal={Journal of Pharmacology and Experimental Therapeutics},
  pages={336 - 348}
  • R. Obach, R. Walsky, L. Tremaine
  • Published 1 January 2006
  • Biology, Medicine, Chemistry
  • Journal of Pharmacology and Experimental Therapeutics
The accuracy of in vitro inhibition parameters in scaling to in vivo drug-drug interactions (DDI) was examined for over 40 drugs using seven human P450-selective marker activities in pooled human liver microsomes. These data were combined with other parameters (systemic Cmax, estimated hepatic inlet Cmax, fraction unbound, and fraction of the probe drug cleared by the inhibited enzyme) to predict increases in exposure to probe drugs, and the predictions were compared with in vivo DDI gathered… 

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