Parameters generated from a kinetic model for the interaction of diclofenac and quinidine with CYP3A45-a
| Reaction | KS15-b | KS25-b | Vmax5-b | Factor5-b | Equation5-b |
|---|---|---|---|---|---|
| μM | nmol/min/nmol | ||||
| Quinidine 3-hydroxylation | 1.3 ± 0.2 | 63.3 ± 9.6 | 5.8 ± 0.3 | 0.6 ± 0.4 | 1 |
| (V maxQ) | (α) | ||||
| Diclofenac 5-hydroxylation | 1.4 ± 0.2 | 54.2 ± 4.5 | 10.5 ± 1.5 | 5.9 ± 0.8 | 2 |
| (V maxD) | (β) | ||||
↵5-a The kinetic model is shown in Fig. 2 and equations are described under Experimental Procedures.
↵5-b VmaxQ andVmaxD are the maximum velocities for the formation of 3-hydroxyquinidine and 5-hydroxydiclofenac, respectively;KS1 is the dissociation constant for E⇌ ES1 and KS2 for E⇌ ES2; α and β are the factors by whichVmax values increase (or decrease) when the second substrate is included in the interaction with the enzyme. Data are presented as mean ± S.E.