Figure 1.
The ketoconazole-induced increases in venetoclax exposure are partially mediated by CYP3A. Plasma concentration curves of venetoclax in (A) female FVB wild-type or (B) CYP3A(−/−) mice administered venetoclax (10 mg/kg; PO) 30 min after ketoconazole (50 mg/kg; PO) or vehicle (PEG400; PO) (n = 5/group). Serial plasma samples were collected from each mouse and analyzed via LC-MS/MS. (C) Maximum concentration (Cmax) and (D) area under the concentration-time curve (AUC) using the last observed timepoint (AUC0–8h) calculated with non-compartmental analysis (NCA) using Phoenix WinNonlin 8.1; * p < 0.05, ** p < 0.01, *** p < 0.001. In a separate experiment, CYP3A(−/−) mice showed significantly greater venetoclax exposure when compared against wild-type FVB mice (Supplementary Figure S2; p = 0.01).