Kinetics of DXM metabolism by individual human cytochrome P450 enzymes
| CYP2D6 | CYP3A4 | CYP2B6 | CYP2C9 | CYP2C19 | CYP2C18 | |
|---|---|---|---|---|---|---|
| RAF (%) (von Moltke et al., 1998) | 2.9 | 56 | N.A. | 30.9 | 10.1 | N.A. |
| APC (%) (McGinnity et al., 2000) | 2 | 30 | 0.21-a | 20 | 4 | N.A. |
| DXO formation | ||||||
| V max (pmol/pmol P450/min) | 11.9 ± 0.7 | 5.4 ± 0.2 | 0.5 ± 0.1 | 3.4 ± 0.2 | 1.3 ± 0.1 | 2.4 ± 0.2 |
| K m (μM) | 3.7 ± 1.2 | 157 ± 26 | 243 ± 79 | 222 ± 49 | 219 ± 35 | 453 ± 91 |
| V max/K m (μl/pmol P450/min) | 3.22 | 0.034 | 0.002 | 0.015 | 0.006 | 0.005 |
| RAF-normalized V max/K m(%) | 79.2 | 16.3 | N.C. | 4 | 0.5 | N.C. |
| APC-normalized V max/K m(%) | 82.6 | 13.2 | N.C. | 3.9 | 0.3 | N.C. |
| MEM formation | ||||||
| V max (pmol/pmol P450/min) | 38.5 ± 7.1 | 21.3 ± 0.9 | 29.9 ± 0.6 | 1.0 ± 0.1 | 1.9 ± 0.1 | 17.2 ± 1.1 |
| K m (μM) | 1290 ± 575 | 232 ± 38 | 105 ± 7 | 343 ± 75 | 237 ± 38 | 354 ± 81 |
| V max/K m (μl/pmol P450/min) | 0.030 | 0.092 | 0.283 | 0.003 | 0.008 | 0.049 |
| RAF-normalized V max/K m(%) | 1.6 | 95.1 | N.C. | 1.6 | 1.7 | N.C. |
| APC-normalized V max/K m(%) | 2 | 92.9 | 1.9 | 1.9 | 1.3 | N.C. |
| HYM formation from DXO | ||||||
| V max (pmol/pmol P450/min) | 10.5 ± 1.3 | 2.6 ± 0.5 | ||||
| K m (μM) | 2640 ± 570 | 724 ± 213 | ||||
| V max/K m (μl/pmol P450/min) | 0.004 | 0.004 | ||||
| HYM formation from MEM | ||||||
| V max (pmol/pmol P450/min) | 4.3 ± 0.1 | 0.13 ± 0.01 | ||||
| K m (μM) | 5.0 ± 0.4 | 49.6 ± 21.1 | ||||
| V max/K m (μl/pmol P450/min) | 0.86 | 0.003 |
RAF and APC of each P450 in human liver were used to analyze their comparative contributions to metabolite formation.
N.C., not calculated; N.A., not available.
↵1-a From Shimada, 1994.