FIG. 5.

Dixon plots for the inhibition of CYP2C9-catalyzed tolbutamide 4-methylhydroxylation (A) and CYP2C19-catalyzed S-mephenytoin 4′-hydroxylation (B) by voriconazole in HLMs. Each substrate probe was incubated with HLMs and cofactors without or with a range of voriconazole concentrations at 37°C for 60 min. Tolbutamide (50 to 500 μM), HLMs (1 mg/ml; HL-09/14/99), and voriconazole (1 to 25 μM) were used for the CYP2C9 assay; and S-mephenytoin (10 to 75 μM), HLMs (0.5 mg/ml; SD-101), and voriconazole (2.5 to 10 μM) were used for the CYP2C19 assay. Each point represents the mean of duplicate measurements.