Enzyme kinetic parameters for cytochrome P450 CYP3A catalyzed reactions in pooled HLMs from *1/*1 and *3/*3 donorsa
| HLM CYP3A5 *1/*1 (EM) | HLM CYP3A5 *3/*3 (PM) | |||||
|---|---|---|---|---|---|---|
| KM ± S.E. | Vmax ± S.E. | CLint | KM ± S.E. | Vmax ± S.E. | CLint | |
| Alprazolam | ||||||
| 1′-Hydroxylation | 240 ± 23 | 0.45 ± 0.10 | 1.9 | 250 ± 12 | 0.20 ± 0.00 | 0.79 |
| 4-Hydroxylation | 800 ± 85 | 4.1 ± 0.2 | 5.1 | 830 ± 53 | 3.6 ± 0.1 | 4.3 |
| Midazolam | ||||||
| 1′-Hydroxylation | 4.3 ± 0.3 | 1.1 ± 0.0 | 260 | 2.9 ± 0.2 | 0.41 ± 0.01 | 140 |
| 4-Hydroxylation | 35 ± 6 | 0.72 ± 0.09 | 21 | 14 ± 3 | 0.30 ± 0.04 | 21 |
| Triazolam | ||||||
| 1′-Hydroxylation | 39 ± 4 | 1.6 ± 0.0 | 42 | 61 ± 6 | 1.8 ± 0.0 | 29 |
| 4-Hydroxylation | 160 ± 14 | 2.2 ± 0.1 | 14 | 170 ± 18 | 2.5 ± 0.1 | 15 |
| Testosterone | ||||||
| 6β-Hydroxylation | 58 ± 4 | 4.5 ± 0.1 | 82 | 40 ± 7 | 3.7 ± 0.2 | 94 |
| Tamoxifen | ||||||
| N-Demethylation | 11 ± 1 | 1.9 ± 0.1 | 170 | 6.3 ± 0.8 | 2.9 ± 0.1 | 460 |
| Atazanavir | ||||||
| Phenyl p-hydroxylation | 7.3 ± 3.3 | 0.12 ± 0.04 | 16 | 4.4 ± 1.8 | 0.044 ± 0.010 | 10 |
| t-Butyl hydroxylation | 7.2 ± 3.3 | 0.15 ± 0.04 | 21 | 4.4 ± 1.9 | 0.077 ± 0.018 | 18 |
CLint, intrinsic clearance; EM, extensive metabolizer; HLMs, human liver microsomes; PM, poor metabolizer.
↵a Units: KM: µM; Vmax: nmol/min/mg; CLint: µl/min/mg.