Steady-state kinetics analysis: CPA, R-IFA, and S-IFA metabolism by cDNA-expressed P450s 3A1, 3A2, 3A7, and 3A12
Data based on two independent determinations (mean values ± half-the-range).
P450 | Drug | 4-Hydroxylation | N-Dechloroethylation | ||||
|---|---|---|---|---|---|---|---|
| Km | Vmax | Km | Vmax | ||||
| mM | mol/min/mol P450 | mM | mol/min/mol P450 | ||||
| 3A1 | CPA | 1.15 ± 0.28 | 10.5 ± 0.5 | 0.69 ± 0.24 | 25.5 ± 2.7 | ||
| R-IFA | 0.22 ± 0.04 | 19.3 ± 0.5 | 0.61 ± 0.16 | 2.5 ± 0.5 | |||
| S-IFA | 0.19 ± 0.03 | 23.1 ± 2.2 | 0.36 ± 0.10 | 2.9 ± 0.2 | |||
| 3A2 | CPA | 1.82 ± 0.34 | 8.5 ± 0.7 | 1.97 ± 0.12 | 28.4 ± 3.8 | ||
| R-IFA | 0.95 ± 0.12 | 23.9 ± 0.4 | 1.19 ± 0.09 | 3.4 ± 0.9 | |||
| S-IFA | 1.10 ± 0.13 | 21.2 ± 0.8 | 1.17 ± 0.06 | 12.5 ± 4.2 | |||
| 3A7 | CPA | 1.04 ± 0.01 | 8.8 ± 1.8 | 2.03 ± 0.74 | 1.6 ± 0.6 | ||
| R-IFA | 1.05 ± 0.05 | 6.0 ± 2.3 | 3.41 ± 1.88 | 1.1 ± 0.3 | |||
| S-IFA | 0.42 ± 0.02 | 4.4 ± 1.8 | 0.57 ± 0.22 | 1.3 ± 0.4 | |||
| 3A12 | CPA | 3.42 ± 0.37 | 24.2 ± 4.8 | 6.78 ± 0.70 | 55.8 ± 18.6 | ||
| R-IFA | 1.83 ± 0.21 | 32.5 ± 8.9 | 5.78 ± 1.33 | 8.5 ± 5.0 | |||
|
| S-IFA | 0.92 ± 0.08 | 14.3 ± 1.4 | 2.89 ± 0.84 | 49.4 ± 19.7 | ||