CYP2D6 Allele | CYP2D6 Protein | Amino Acid Changes | O-Demethylation | 7-Hydroxylationa | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Km | Vmax | Vmax/Km | Km | Vmax | Vmax/Km | |||||||
μM | nmol/min/nmol CYP2D6 | ml/min/nmol CYP2D6 | μM | nmol/min/nmol CYP2D6 | ml/min/nmol CYP2D6 | |||||||
* 1 | CYP2D6.1 | None | 10 ± 1 | 6.3 ± 0.9 | 0.63 | N.D. | N.D. | N.D. | ||||
* 10 | CYP2D6.10 | P34S, S486T | 63 ± 7 | 1.2 ± 0.2** | 0.019 | N.D. | N.D. | N.D. | ||||
* 49 | CYP2D6.49 | P34S, F120I, S486T | 323 ± 44**,‡ | 0.9 ± 0.1** | 0.003 | 391 ± 23 | 0.8 ± 0.2 | 0.002 | ||||
*
72
| CYP2D6.72 | P34S, E383K, S486T | 87 ± 21* | 0.7 ± 0.3**,† | 0.008 | N.D. | N.D. | N.D. |
N.D., product not detectable.
↵ a Hydroxylation velocity was determined as the peak area ratio of metabolite to dextrorphan standard.
↵* P < 0.05 and ** P < 0.01, significantly different from wild-type CYP2D6*1 by Dunnett's test.
↵† P < 0.05 and ‡P < 0.01, significantly different from CYP2D6*10 by Dunnett's test.