TABLE 2.
Kinetic parameters for the rCYP3A4- and rCYP3A5-catalyzed metabolism of MDZ, TST, terfenadine, and vincristine
Data are presented as the mean ± S.D. (n = 3 determinations), except for the CYP3A5/CYP3A4 Vmax/Km (S50) ratio.
| P450 | Substrate | Model | Km (S50) | Vmaxa | nb | Vmax/Km(S50) | Vmax/Km (S50) Ratioc |
|---|---|---|---|---|---|---|---|
| µM | |||||||
| CYP3A4 | MDZ | Hyperbolic | 1.8 ± 0.3 | 19 ± 1 | — | 11.0 | |
| TST | Sigmoidal | 78 ± 34 | 86 ± 3 | 1.2 ± 0.13 | 1.1 | ||
| Terfenadine | Hyperbolic | 3.4 ± 0.4 | 24 ± 2 | — | 7 | ||
| Vincristine | Sigmoidal | 75 ± 22 | 15 ± 4 | 1.5 ± 0.15 | 0.2 | ||
| CYP3A5 | MDZ | Hyperbolic | 3.0 ± 0.5 | 35 ± 2 | — | 11.7 | 1.1 |
| TST | Hyperbolic | 67 ± 13 | 56 ± 4 | — | 0.8 | 0.7 | |
| Terfenadine | Hyperbolic | 1.5 ± 0.2 | 18 ± 1 | — | 12.0 | 1.7 | |
| Vincristine | Sigmoidal | 47 ± 6.7 | 70 ± 7 | 1.5 ± 0.11 | 1.5 | 7.5 |
a
Presented as pmol/min/pmol P450, except for the formation of vincristine M1 metabolite. No attempt was made to formally quantitate M1, so data are presented as arbitrary units (see Materials and Methods).
b
Hill coefficient.
c
Ratio of CYP3A5 Vmax/Km (S50) versus CYP3A4 Vmax/Km (S50).