Effect of allelic differences on CYP2C8-mediated paclitaxel metabolism
Metabolism of paclitaxel by E. coli membrane fractions coexpressing CYP2C8 variants and P450 reductase. Data were not consistent with Michaelis-Menten kinetics due to substrate inhibition at concentrations >15 μM paclitaxel. Formation of 6α-hydroxy paclitaxel over a period of 30 min at 10 μM paclitaxel was determined. Values are expressed as means ± S.D. for four independent experiments performed with the same batch of enzymes.
| CYP2C8 Variant | 6α-OH Paclitaxel |
|---|---|
| nmol/(min · nmol) P450 | |
| CYP2C8.1 | 6.4 ± 2.3 |
| CYP2C8.1 (R139K) | 4.4 ± 2.1 |
| CYP2C8.1 (K399R) | 3.4 ± 2.0 |
| CYP2C8.3 | 7.1 ± 3.0 |
| CYP2C8.4 | 7.0 ± 2.6 |