TABLE 6

In vitro hepatic intrinsic clearance of AKP-001 and its metabolites

Compounds	CL_{int, S9}	f_S9^a	CL_{int,u,in vitro}^b	f_b·CL_{int,u,in vitro}^c
	μl/min/mg protein		l/h/kg	l/h/kg
AKP-001	91.4	0.577 ± 0.074	36.5	2.47
M1	31.2	0.801 ± 0.022	8.99	1.37
M2	56.8	0.803 ± 0.058	16.3	0.282

↵^a Unbound fraction at 1 μM
↵^b The unbound intrinsic clearance was extrapolated by correcting with unbound fraction in liver S9 fractions, the physiologic scaling factor of 96.1 mg S9 protein/g liver (Watanabe et al., 2009), and 40 g liver/kg body weight (Davies and Morris, 1993).
↵^c The blood-unbound fraction (f_b) was calculated as f_p/R_b.