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 CL_int values, scaled CL_int,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	CL_int	CL_{int, H}	Predicted f_{m,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