Kinetic characteristics for diazepam metabolism by human 2C P450s 1-a
| Diazepam N-Demethylation | Diazepam 3-Hydroxylation | |
|---|---|---|
| P4502C8 | ND1-b | ND |
| P4502C9 | ||
| V max(min−1) | 0.96 ± 0.13 | ND |
| KM (μM) | 80 ± 15 | |
| V max/KM (min−1 μM−1) | 0.013 | |
| P4502C18 | ||
| V max(min−1) | 1.11 ± 0.06 | ND |
| KM (μM) | 24 ± 4 | |
| V max/KM (min−1 μM−1) | 0.047 | |
| P4502C19 | ||
| V max(min−1) | 1.76 ± 0.07 | 0.58 ± 0.03 |
| KM (μM) | 21 ± 3 | 21 ± 9 |
| V max/KM (min−1μM−1) | 0.084 | 0.031 |
↵1-a Kinetic parameters (Vmax and KM , ± SD,N = 3) were estimated by nonlinear regression analysis of the velocity vs. substrate concentration plots (concentration range: 5–200 μM diazepam for 2C18 and 2C19; 5–500 μM for 2C9).
↵1-b ND, Not detected (rates < 0.03 min−1 at 100 μM substrate concentration).