Michaelis-Menten kinetic constants for the N-desmethylclobazam formation by cDNA-expressed CYP3A4, CYP2C19, and CYP2B6 and the 4′-hydroxy-N-desmethylclobazam formation by cDNA-expressed CYP2C19 Values are mean ± S.D.; each mean was obtained from three experiments in duplicate.
cDNA-Expressed | |||||
|---|---|---|---|---|---|
| CYP3A4 | CYP2C19 | CYP 2B6 | |||
| N-Desmethyclobazam (NCLB) formation | |||||
| Apparent Km (μM) | 29.0 ± 2.9 | 31.9 ± 2.9 | 289 ± 39 | ||
| Vmax (nmol/min/nmol P450) | 6.20 ± 0.23 | 1.15 ± 0.04 | 5.70 ± 0.29 | ||
| CLint (μl/min/nmol P450) | 214 | 36.1 | 19.7 | ||
| 4′-Hydroxy-N-desmethylclobazam (OH-NCLB) formation | |||||
| Apparent Km (μM) | 5.74 ± 0.87 | ||||
| Vmax (nmol/min/nmol P450) | 0.219 ± 0.020 | ||||
| CLint (μl/min/nmol P450) | 38.2 | ||||
| Hill coefficient |
| 1.54 |
| ||
Km, Michaelis constant, Vmax, maximum rate of formation, CLint, intrinsic clearance (CLint = Vmax/apparent Km).