TABLE 6

Hepatic P450 content-based normalization of recombinant P450 CL_int of LY2452473 as determined by LY2452473 depletion

CL_int of substrate depletion was calculated by k_dep × incubation volume per picomole of rP450. Normalized CL_int was calculated by multiplying CL_int by reported hepatic specific content from Rodrigues (1999) and Lee et al. (2010). f_m was calculated by summing relevant normalized CL_int and dividing normalized CL_int for an individual rP450 by the relevant total (× 100).

Enzyme	CL_int	Specific Content	Normalized CL_int	f_m Relative to Total Normalized CL_int
	μl · min⁻¹ · pmol P450⁻¹	pmol P450/mg protein	μl · min⁻¹ · mg protein⁻¹	%
CYP2C9	0.10	96	10	8.5
CYP2C19	0.30	19	5.7	4.9
CYP2D6	0.30	10	3.0	2.6
CYP2J2	1.79	10	18	15
CYP3A4	0.75	108	80	68
Total			117	100