Enzyme kinetic parameters for the hydroxylation of midazolam by recombinant CYP3A enzymes
Km and Vmax were calculated by fitting data to a substrate inhibition model (v = Vmax[S]/Km + [S] + Km[S]2/Ki) equation using nonlinear regression analysis and SigmaPlot 7.1 (SPSS Science).
Enzyme | Midazolam 1′-Hydroxylation | ||||||
|---|---|---|---|---|---|---|---|
| Vmax
a
| Km
b
| CLintc | Ki
d
| ||||
| CYP3A64 | 6.2 ± 0.2 | 1.4 ± 0.2 | 4.3 | 306 ± 44 | |||
| CYP3A4 | 4.7 ± 0.2 | 1.9 ± 0.2 | 2.6 | 383 ± 46 | |||
| CYP3A12 | 5.8 ± 0.2 | 0.9 ± 0.1 | 6.3 | 117 ± 19 | |||
| CYP3A26 | 0.6 ± 0.0 | 98.3 ± 14.1 | <0.1 | NA | |||
| CYP3A2 | 4.0 ± 0.2 | 2.0 ± 0.3 | 2.0 | 167 ± 23 | |||
| CYP3A1 | 5.1 ± 0.3 | 1.2 ± 0.2 | 4.2 | 41 ± 5 | |||
| CYP3A6 | 0.8 ± 0.0 | 0.9 ± 0.1 | 0.9 | 100 ± 32 | |||