Kinetic parameters for oxidation activities of coumarin, 7-ethoxycoumarin, and phenacetin by marmoset P450 2A6 and liver microsomes (LM) and corresponding enzymes in cynomolgus monkeys (C) and humans (H)
Kinetic parameters were calculated by nonlinear regression analysis (mean ± S.E.).
| Drug Oxidation | Enzyme Source | Km | Vmax | Vmax | Vmax/Km | Vmax/Km |
|---|---|---|---|---|---|---|
| μM | min−1 | pmol/min/mg | μl/min/nmol | μl/min/mg | ||
| Coumarin | Marmoset 2A6 | 192 ± 48 | 0.053 ± 0.004 | 0.28 | ||
| 7-Hydroxylation | Cynomolgus 2A23a | 0.3 ± 0.1 | 0.4 ± 0.1 | 1300 | ||
| Cynomolgus 2A24a | 6.4 ± 1.5 | 9.9 ± 1.1 | 1500 | |||
| Cynomolgus 2A26a | 0.5 ± 0.1 | 1.4 ± 0.1 | 2800 | |||
| Human 2A6a | 0.6 ± 0.1 | 5.6 ± 0.4 | 9300 | |||
| Human 2A13 | 0.5 ± 0.1 | 0.3 ± 0.1 | 610 | |||
| MLM | 253 ± 43 | 6.8 ± 0.4 | 0.03 | |||
| CLM | 5.3 ± 0.3 | 636 ± 13 | 120 | |||
| HLM | 2.0 ± 0.1 | 557 ± 10 | 280 | |||
| 7-Ethoxycoumarin | Marmoset 2A6 | 13 ± 3 | 3.9 ± 0.2 | 300 | ||
| O-Deethylation | Cynomolgus 2A23 | 6.1 ± 0.7 | 11 ± 1 | 1800 | ||
| Cynomolgus 2A24 | 50 ± 7 | 4.9 ± 0.2 | 98 | |||
| Cynomolgus 2A26 | 26 ± 5 | 7.8 ± 0.4 | 300 | |||
| Human 2A6 | 98 ± 12 | 1.9 ± 0.1 | 19 | |||
| Human 2A13 | 40 ± 6 | 66 ± 4 | 1700 | |||
| MLM | 16 ± 1 | 643 ± 10 | 40 | |||
| CLM | 16 ± 1 | 1550 ± 32 | 97 | |||
| HLM | 14 ± 1 | 642 ± 11 | 46 | |||
| Phenacetin | Marmoset 2A6 | 102 ± 12 | 9.4 ± 0.5 | 92 | ||
| O-Deethylation | Cynomolgus 2A23 | 72 ± 6 | 4.1 ± 0.1 | 57 | ||
| Cynomolgus 2A24 | NA | <0.1 | NA | |||
| Cynomolgus 2A26 | NA | <0.1 | NA | |||
| Human 2A6 | NA | <0.1 | NA | |||
| Human 2A13 | 33 ± 4 | 9.6 ± 0.6 | 290 | |||
| MLM | 23 ± 2 | 270 ± 10 | 12 | |||
| CLM | 174 ± 3 | 937 ± 10 | 5.4 | |||
| HLM | 54 ± 16 | 391 ± 79 | 7.2 |
NA, not available.
↵a Kinetic parameters for coumarin 7-hydroxylation by human P450 2A6 are taken from Uehara et al. (2011).