Table 1

Effect of active microsomal protein concentration on inhibitory effect of CYP3A inhibitors, based on diazepam 3-hydroxylation as an index reaction

Inhibitor (μM)Mean (± S.E.) Fraction (Rv) of Control (Uninhibited) Diazepam 3-Hydroxylation Velocity at Protein ConcentrationFree IC501-150
0.06250.1250.250.50.751.02.03.0
mg/ml μM
Ritonavir (0.05)0.21  ± 0.090.27  ± 0.120.45  ± 0.110.61  ± 0.130.67  ± 0.090.72  ± 0.080.86  ± 0.050.92  ± 0.040.0035  ± 0.0016
Ketoconazole (0.05)0.24  ± 0.040.21  ± 0.050.44  ± 0.140.53  ± 0.110.61  ± 0.090.70  ± 0.080.83  ± 0.060.89  ± 0.030.0059  ± 0.0028
OH-Itraconazole (0.25)0.32  ± 0.050.37  ± 0.100.37  ± 0.060.45  ± 0.060.55  ± 0.040.59  ± 0.060.76  ± 0.070.79  ± 0.050.095  ± 0.01
Itraconazole (1.0)0.23  ± 0.020.23  ± 0.020.29  ± 0.020.32  ± 0.020.43  ± 0.040.49  ± 0.040.63  ± 0.060.82  ± 0.030.19  ± 0.05
Norfluoxetine (25)0.26  ± 0.030.18  ± 0.010.32  ± 0.030.40  ± 0.040.47  ± 0.040.57  ± 0.040.73  ± 0.010.83  ± 0.034.3  ± 1.3
Fluvoxamine (50)0.49  ± 0.050.48  ± 0.080.48  ± 0.060.50  ± 0.010.58  ± 0.060.69  ± 0.050.75  ± 0.030.83  ± 0.0537.4  ± 4.7
Fluconazole (10)0.33  ± 0.020.36  ± 0.030.37  ± 0.060.44  ± 0.070.51  ± 0.060.51  ± 0.070.52  ± 0.040.54  ± 0.06

Table entries (Rv values) are defined from eq. 1 in text.

  • ↵1-150  Parameter estimate ± standard error of estimate from nonlinear regression, based on eq. 5 in text.