Table 2.
Inhibitory types and kinetic constants of valproic acid for human CYP activities
| CYP | Kia (µm) [KI,Kinact]b | Type of inhibition |
|---|---|---|
| CYP2A6 | 12372 (αc = 3.2) | mixed |
| [9150 µm, 0.048 min−1]b | [mechanism-based] | |
| CYP2C9 | 600 | competitive |
| CYP2C19 | 8553 (αc = 2.5) | mixed |
| CYP3A4 | 7975 | competitive |
a
Values are derived from nonlinear regression analysis based on coincubation of the respective CYP specific substrates with various concentrations of valproic acid without preincubation at 37 ° C (see the Methods and Table 1 for details).
b
Inhibition of CYP2A6 was preincubation-time dependent. The parameters for mechanism-based inhibition are given in parenthesis (see Methods for details).
c
The factor by which Km changes when inhibitor occupies the enzyme site.