TABLE 4

Scaling of in vitro CL_int to project contributions of CYP2B6, CYP2C9, CYP2C19, and CYP3A to in vivo clearance of R-95913 via R-138727

Scaling Determination	P450s	Literature References	Abundance	Contribution to R-95913 Clearance^a
			pmol/mg	%
A	CYP2B6	Hijazi and Boulieu, 2002	4.8	6
	CYP2C9	Lasker et al., 1998; Hijazi and Boulieu, 2002	89	19
	CYP2C19	Lasker et al., 1998	18	11
	CYP3A	Hijazi and Boulieu, 2002	146	64
B	CYP2B6	Rodrigues et al., 1999	39	32
	CYP2C9	Lasker et al., 1998; Hijazi and Boulieu, 2002	89	14
	CYP2C19	Lasker et al., 1998	18	8
	CYP3A	Hijazi and Boulieu, 2002	146	46
C	CYP2B6	Shimada et al., 1994	1.0	2
	CYP2C9	Shimada et al., 1994; Lasker et al., 1998 ^b	50	18
	CYP2C19	Shimada et al., 1994; Lasker et al., 1998 ^b	10	10
	CYP3A	Shimada et al., 1994	96	70
D^c	CYP2B6	Shimada et al., 1999	7.8	14
	CYP2C9	Lasker et al., 1998; Shimada et al., 1999 ^b	55	19
	CYP2C19	Lasker et al., 1998; Shimada et al., 1999 ^b	11	11
	CYP3A	Shimada et al., 1999	78	55
E	CYP2B6	Rodrigues et al., 1999	39	36
	CYP2C9	Rodrigues et al., 1999	96	17
	CYP2C19	Rodrigues et al., 1999	19	9
	CYP3A	Rodrigues et al., 1999	108	38
			Range of Contributions (%)
	CYP2B6		2-36
	CYP2C9		14-19
	CYP2C19		8-11
	CYP3A4		38-70

↵ a CL_int values from Table 2 were scaled according to eqs. 3 and 4 under Materials and Methods to determine contributions.
↵ b The abundances of total CYP2C from Shimada et al. (1994) and Shimada et al. (1999) were adjusted by the proportions of CYP2C9 and CYP2C19 (5 parts to 1 part) reported in Lasker et al. (1998).
↵ c Shimada et al. (1999) data for the livers of Caucasian origin only.