Table 2.
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 |
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).
Inhibition of CYP2A6 was preincubation-time dependent. The parameters for mechanism-based inhibition are given in parenthesis (see Methods for details).
The factor by which Km changes when inhibitor occupies the enzyme site.