TABLE 2

Kinetics of R- and S-bupropion metabolism in human liver S9 fractions

Substrate and Metabolites	CL_int	CL_int,H^{^a}	f_m,enantiomer^{^b}	f_m^{^c}
	μl/min/mg S9 protein	l/h
R-bupropion
R,R-OH-bupropion	0.47	4.1	0.34	0.17
R,R-threohydrobupropion	0.69	6.0	0.50	0.25
S,R-erythrohydrobupropion	0.11	0.9	0.08	0.04
4′-OH-bupropion	0.11	0.9	0.08	0.04
Total R-bupropion CL_int		11.9
S-bupropion
S,S-OH-bupropion	0.81	7.0	0.12	0.06
S,S-threohydrobupropion	5.61	48.5	0.82	0.41
R,S-erythrohydrobupropion	0.25	2.1	0.04	0.02
4′-OH-bupropion	0.13	1.1	0.02	0.01
Total S-bupropion CL_int		59.2

↵^a S9 fraction intrinsic clearance values were scaled to CL_int,H using the scaling factor of 96.1 mg S9 protein/g liver (Watanabe et al., 2009). Assuming body weight of 70 kg and 21.4 g liver/kg body weight results in 1500 g liver weight (Ito and Houston, 2005). Protein binding in the incubations was negligible, and unbound fractions in the incubations were assumed to be 1.
↵^b The fraction metabolized to each metabolite from the individual bupropion enantiomer (f_{m, enantiomer}) calculated from CL_int,H data.
↵^c The fraction of racemic bupropion metabolized to the specific metabolite (f_m).