TABLE 1.
Kinetic parameters for (S,S)- and (R,R)-hydroxybupropion formation from RS-bupropion by CYP2B6 variants
| CYP2B6 variant | (S,S)-hydroxybupropion formation from RS-bupropion | (R,R)-hydroxybupropion formation from RS-bupropion | ||||
|---|---|---|---|---|---|---|
| Vmax | Km | Clinta | Vmax | Km | Clinta | |
| pmol/min per picomole | µM | ml/min per nanomole | pmol/min per picomole | µM | ml/min per nanomole | |
| CYP2B6.1 | 26.4 ± 0.5 | 18.2 ± 1.5 | 1.45 (100) | 9.0 ± 0.1 | 11.4 ± 0.8 | 0.79 (100) |
| CYP2B6.4 | 23.5 ± 0.4 | 14.5 ± 1.0 | 1.62 (112) | 8.0 ± 0.1 | 9.3 ± 1.6 | 0.86 (109) |
| CYP2B6.5 | 14.4 ± 0.2 | 17.3 ± 0.8 | 0.83 (57) | 5.1 ± 0.1 | 12.2 ± 0.7 | 0.42 (53) |
| CYP2B6.6 | 39.0 ± 0.6 | 53.0 ± 2.7 | 0.74 (51) | 10.8 ± 0.2 | 39.3 ± 2.0 | 0.27 (34) |
| CYP2B6.7 | 15.6 ± 0.2 | 31.1 ± 1.5 | 0.50 (34) | 3.7 ± 0.1 | 21.4 ± 1.5 | 0.17 (22) |
| CYP2B6.9 | 20.7 ± 0.2 | 53.3 ± 2.1 | 0.39 (27) | 6.0 ± 0.6 | 37.7 ± 1.3 | 0.16 (20) |
| CYP2B6.16b | 0.74 ± 0.03 | 0.72 ± 0.02 | ||||
| CYP2B6.17 | 22.3 ± 1.1 | 21.3 ± 2.5 | 1.05 (72) | 11.8 ± 0.2 | 13.1 ± 0.8 | 0.90 (114) |
| CYP2B6.18b | 0.91 ± 0.03 | 0.78 ± 0.01 | ||||
| CYP2B6.19 | 49.2 ± 4.1 | 75.6 ± 11.0 | 0.65 (45) | 16.2 ± 0.2 | 45.4 ± 2.1 | 0.36 (46) |
| CYP2B6.26 | 31.7 ± 2.1 | 41.5 ± 5.3 | 0.76 (52) | 8.5 ± 0.1 | 22.0 ± 1.4 | 0.39 (49) |
a
Values in brackets represent percentages of CYP2B6.1 Clint.
b
For CYP2B6.16 and CYP2B6.18, rates were measured at a fixed substrate concentration of 1000 µM RS-bupropion.