Cytochrome P450 | Inhibitor | Type of Inhibition | Km | Vmax6-a | Ki |
---|---|---|---|---|---|
μM | pmol/min/mg | μM | |||
CYP1A2 | None | None | 0.25 ± 0.03 | 118 ± 4 | |
Org OD14 | Competitive | 100 | |||
Org 4094 | Competitive | 245 | |||
Org 30126 | Competitive | 640 | |||
Org OM38 | Competitive | 775 | |||
Fluvoxamine | Noncompetitive | 0.33 ± 0.04 | 126 ± 6 | 0.21 ± 0.02 | |
CYP2C9 | None | None | 12.6 ± 0.8 | 3178 ± 65 | |
Org OD14 | Competitive | 12.3 ± 1.2 | 3089 ± 94 | 14.8 ± 1.7 | |
Org 4094 | Competitive | 12.2 ± 1.1 | 3081 ± 86 | 17.4 ± 1.9 | |
Org 30126 | Competitive | 13.1 ± 0.9 | 3168 ± 64 | 84.2 ± 14.3 | |
Org OM38 | Competitive | 12.8 ± 1.4 | 3256 ± 108 | 32.9 ± 5.3 | |
Sulfaphenazole | Competitive | 14.3 ± 2.2 | 3283 ± 161 | 0.28 ± 0.05 | |
CYP2E1 | None | None | 238 ± 29 | 2047 ± 119 | |
Diethyldithiocarbamate | Noncompetitive | 230 ± 18 | 1990 ± 74 | 33.0 ± 2.6 | |
CYP3A | None | None | 62.7 ± 8.1 | 9464 ± 393 | |
Org OD14 | Competitive | 62.5 ± 8.0 | 9490 ± 396 | 14.5 ± 2.0 | |
Org 4094 | Competitive | 61.8 ± 7.1 | 9474 ± 350 | 3.57 ± 0.39 | |
Org 30126 | Competitive | 63.3 ± 7.0 | 9557 ± 347 | 6.05 ± 0.67 | |
Org OM38 | Noncompetitive | 56.3 ± 9.7 | 4727 ± 331 | 62.8 ± 8.8 | |
0.05 μM ketoconazole | Competitive6-b | 64.0 ± 9.1 | 9569 ± 449 | 0.017 ± 0.003 | |
0.2 μM ketoconazole | Competitive6-b | 65.7 ± 8.3 | 9683 ± 410 | 0.020 ± 0.003 |
Results are presented as means ± S.D.
↵6-a Km andVmax values given for incubations in the presence of Org OD14, Org 4095, Org 30126, Org OM38, or a model inhibitor represent back-calculated values in the EZ-FIT curve-fitting program and are only indicative of a goodness of fit.
↵6-b The best fit for ketoconazole was obtained with the competitive inhibition model. However, data showed that the metabolism of testosterone in the presence of ketoconazole has a sigmoidal nature. Therefore, the type of CYP3A4 inhibition by ketoconazole is not clear.