Perpetrator Drug | Dose | Predicted Fold Increase in AUC Due to Inhibition of Composite Pathways | Overall Predicted Fold Increase in AUC | Clinically Observed Fold Increase in AUC | Reference | Primary Mechanism of DDI | |
---|---|---|---|---|---|---|---|
Intestinal BCRP (Theoretical Max = 2.0) | OATP1B1 (Theoretical Max = 1.6) | ||||||
mg | |||||||
Fostamatinib/R406 | 100 | 2.00 | 1.01 | 2.02 | 1.96 | Martin et al. (2016) | BCRP inhibition |
Eltrombopaga | 75 | 1.87 | 1.03 | 1.93 | 1.88 | Allred et al. (2011) | BCRP inhibition |
Darunavir | 600 | 1.33 | 1.09 | 1.45 | 1.48 | Samineni et al. (2012) | BCRP inhibition |
Lopinavir | 400 | 1.71 | 1.25 | 2.14 | 2.10 | Kiser et al. (2008) | BCRP inhibition |
Clopidogrel | 75 | 1.38 | 1.06 | 1.46 | 1.40 | Pinheiro et al. (2012) | BCRP inhibition |
Clopidogrel | 300 | 1.71 | 1.18 | 2.02 | 1.96 | Pinheiro et al. (2012) | BCRP inhibition |
Ezetimibe | 10 | 1.29 | 1.01 | 1.30 | 1.21 | Kosoglou et al. (2004) | BCRP inhibition |
Fenofibrate/fenofibric acid | 67 | 1.15 | 1.01 | 1.16 | 1.07 | Martin et al. (2003) | NA |
Fluconazole | 200 | None | None | 1.10b | 1.14 | Cooper 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).