Compounds | CLint, S9 | fS9a | CLint,u,in vitrob | fb·CLint,u,in vitroc |
---|---|---|---|---|
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 (fb) was calculated as fp/Rb.