Kinetic parameters for the in vitro interaction of quinidine and various CYP3A4 substrates in human recombinant CYP3A4 generated by multisite kinetic model approach (mean ± S.E.)
| CYP3A4 Substrate | Vmax | Ks | Ki | Ka | α | γ | δ |
|---|---|---|---|---|---|---|---|
| pmol/min/pmol P450 | μM | ||||||
| NIF4-a | 7.25 ± 1.24 | 16.7 ± 5.4 | 5.3 ± 2.4 | 0.81 ± 0.25 | 0.16 ± 0.03 | ||
| TSTb | 8.27 ± 0.17 | 260 ± 35 | 99 ± 7 | 0.03 ± 0.01 | |||
| MDZc | 10.5 ± 2.1 | 14.5 ± 1.8 | 14.9 ± 2.7 | 1.8 ± 0.2 | 0.31 ± 0.11 | ||
| FELd | 5.44 ± 0.18 | 52.8 ± 4.4 | 288 ± 75 | 9.8 ± 3.6 | 0.08 ± 0.04 | ||
| SVd | 11.9 ± 0.6e | 80 ± 10 | 226 ± 65 | 2.6 ± 0.8 | 0.16 ± 0.05 |
The kinetic parameters were determined using two-site model:
↵4-a eq. 3, β (SES) = 0.45 ± 0.11 anddeq. 2; the kinetic parameters were determined using the three-site model: beq. 4 and ceq. 6 β (Kp1 from S2ES1) = 0.29 ± 0.08, Ks2 (4-OH MDZ site) = 22.6 ± 3.1 μM; earbitrary number due to the lack of metabolite standards.