Predicted versus observed AUC changes of rosuvastatin with various coadministered drugs based upon inhibition of intestinal BCRP (fe = 0.5) or hepatic OATP1B1 (fe = 0.38) transport

Perpetrator DrugDosePredicted Fold Increase in AUC Due to Inhibition of Composite PathwaysOverall Predicted Fold Increase in AUCClinically Observed Fold Increase in AUCReferencePrimary Mechanism of DDI
Intestinal BCRP (Theoretical Max = 2.0)OATP1B1 (Theoretical Max = 1.6)
Fostamatinib/R4061002. et al. (2016)BCRP inhibition
Eltrombopaga751.871.031.931.88Allred et al. (2011)BCRP inhibition
Darunavir6001.331.091.451.48Samineni et al. (2012)BCRP inhibition
Lopinavir4001.711.252.142.10Kiser et al. (2008)BCRP inhibition
Clopidogrel751.381.061.461.40Pinheiro et al. (2012)BCRP inhibition
Clopidogrel3001.711.182.021.96Pinheiro et al. (2012)BCRP inhibition
Ezetimibe101.291.011.301.21Kosoglou et al. (2004)BCRP inhibition
Fenofibrate/fenofibric acid671. et al. (2003)NA
Fluconazole200NoneNone1.10b1.14Cooper et al. (2002)CYP2C9 inhibition
  • NA, not applicable.

  • a The clinically observed fold-increase in exposure used for comparison with the prediction is the mean AUC change derived from non-Asian subjects within the clinical interaction study.

  • b Based upon inhibition of CYP2C9 (fe = 0.10, fluconazole CYP2C9 Ki = 7 μM; Kunze et al., 1996).