Table 5

Dependence of IC50 values on substrate concentration

Part A. Dependence of IC50 on Substrate Concentration—BQ
Inhibitor10 μM Substrate20 μM Substrate40 μM Substrate
Nifedipine23.7  ± 2.319.8  ± 1.919.5  ± 2.4
Midazolam5.2  ± 2.54.2  ± 1.64.5  ± 0.9
Cisapride0.063  ± 0.0290.051  ± 0.0230.080  ± 0.031
Cyclosporin A3.0  ± 0.26.3  ± 169  ± 12
Itraconazole0.27  ± 0.110.28  ± 0.070.48  ± 0.09
Verapamil1.1  ± 0.23.1  ± 0.616  ± 2
Terfenadine>5015  ± 210  ± 3
Ketoconazole0.034  ± 0.0020.041  ± 0.0020.061  ± 0.007
Part B. Dependence of IC50 on Substrate Concentration—BFC
Inhibitor10 μM Substrate20 μM Substrate50 μM Substrate
Nifedipine7.9  ± 3.46.7  ± 2.56.1  ± 1.4
Midazolam0.38  ± 0.030.39  ± 0.200.33  ± 0.05
Cisapride0.025  ± 0.0070.025  ± 0.0060.032  ± 0.013
Cyclosporin A1.4  ± 11.8  ± 1.15.1  ± 3.7
Itraconazole0.047  ± 0.0060.036  ± 0.0110.040  ± 0.006
Verapamil0.17  ± 0.050.21  ± 0.050.50  ± 0.05
Terfenadine1.4  ± 0.60.76  ± 0.241.0  ± 0.3
Ketoconazole0.0073  ± 0.00120.0077  ± 0.00180.0095  ± 0.0020
Part C. Dependence of IC50on Substrate Concentration—DBF
Inhibitor0.25 μM Substrate0.5 μM Substrate1 μM Substrate
Nifedipine2.3  ± 0.22.5  ± 0.32.8  ± 0.7
Midazolam0.61  ± 0.231.4  ± 0.51.12  ± 0.04
Cisapride0.14  ± 0.050.38  ± 0.090.50  ± 0.07
Cyclosporin A0.98  ± 0.291.5  ± 0.52.2  ± 0.5
Itraconazole0.071  ± 0.0190.065  ± 0.0080.064  ± 0.006
Verapamil1.2  ± 0.12.1  ± 0.44.2  ± 1.1
Terfenadine0.46  ± 0.020.91  ± 0.071.4  ± 0.1
Ketoconazole0.0015  ± 0.00030.001  ± 0.00020.0017  ± 0.0002

Values are the mean ± the standard deviation for two to three independent determinations performed in either duplicate or quadruplicate. Incubation times and enzyme concentrations were as specified under Experimental Procedures.