Parameters generated from a kinetic model for the interaction of diclofenac and quinidine with CYP3A47-a
| Reaction | KS1 7-b | KS2 7-b | Factor7-b δ | Vmax 7-b | Factor7-b | Equation7-b |
|---|---|---|---|---|---|---|
| mM | μM | pmol/min/mg | ||||
| R-Warfarin 10-hydroxylation | 0.3 ± 0.1 | 18.2 ± 3.5 | 0.8 ± 0.2 | 119 ± 13 (V max W) | 5.9 ± 0.8 (α) | 1 |
| Quinidine 3-hydroxylation | 0.3 ± 0.1 | 25.3 ± 2.8 | 0.5 ± 0.2 | 156 ± 6 (V max Q) | 0.7 ± 0.2 (β) | 2 |
↵7-a The kinetic model is shown in Fig. 2 and equations are described under Experimental Procedures.
↵7-b V max Wand V max Q are the maximum velocities for the 10-hydroxylation of R-warfarin and 3-hydroxylation of quinidine, respectively; K S1 is the dissociation constant for E ⇌ ES 1 andK S2 for E ⇌ ES 2; δ, α, and β are the factors by which K S1 (orK S2), k 1, andk 2 are influenced upon binding of a second substrate to the enzyme. Data are presented as mean ± standard error.