Kinetic parameters for the formation of 10-hydroxywarfarin in rabbit liver microsomal incubations containing quinidine The equations from which the kinetic parameters are derived were described under Materials and Methods.
Quinidine | KW a | KQ a | VmaxW a | βa | CLintWb | Equation |
|---|---|---|---|---|---|---|
| μM | μM | μM | pmol / min / mg | μl / min / g | ||
| 0 | 156 ± 27 | 42 ± 3 | 6 ± 1 | 3 and 5 | ||
| 5—100 | 124 ± 11 | 16 ± 2 | 63 ± 24 | 17 ± 6 | 128 ± 51 | 1 and 4 |
↵ a VmaxW is the maximum velocity for the formation of 10-hydroxywarfarin; KW and KQ are the dissociation constants for enzyme-warfarin and enzyme-quinidine complexes respectively; β is the factor by which VmaxW increases when quinidine interacts with the enzyme. Data are presented as mean ± standard derivation
↵ b CLintW denotes the hepatic intrinsic clearance of R-warfarin via the 10-hydroxylation pathway at 0 and 21 μM unbound quinidine, respectively. Data are presented as mean ± standard derivation