TABLE 1.
In vitro intrinsic clearance values for R-bupropion, S-bupropion, threohydrobupropion, and erythrohydrobupropion metabolism with recombinant P450s
Those enzymes found to form the metabolites of interest in a screen with a panel of P450 supersomes were evaluated. In vitro CLint values, scaled CLint,H values, and the fractional contributions of each P450 to the given metabolite formation were calculated as described in Materials and Methods.
| Substrate and Metabolite | Enzyme | CLint | CLint, H | Predicted fm,CYP,metabolite |
|---|---|---|---|---|
| μl/min/nmol P450 | l/h | |||
| R-bupropion | ||||
| R,R-OH-bupropion | CYP2B6 | 69.0 | 3.6 | 0.90 |
| CYP2C19 | 0.9 | 0.1 | 0.03 | |
| CYP3A4 | 0.5 | 0.3 | 0.08 | |
| 4′-OH-bupropion | CYP2C19 | 18.6 | 1.1 | 1 |
| S-bupropion | ||||
| S,S-OH-bupropion | CYP2B6 | 125.0 | 6.6 | 0.89 |
| CYP2C19 | 11.5 | 0.7 | 0.09 | |
| CYP3A4 | 0.1 | 0.1 | 0.01 | |
| 4′-OH-bupropion | CYP2C19 | 17.7 | 1.1 | 1 |
| Erythrohydrobupropion | ||||
| Erythro-4′-OH-hydrobupropion | CYP2C19 | 10.1 | 0.6 | 1 |
| Threohydrobupropion | ||||
| Threo-4′-OH-hydrobupropion | CYP2C19 | 42.3 | 2.6 | 1 |