Extrapolation of the in vivo hepatic uptake clearance from the uptake clearance obtained using isolated hepatocytes and its comparison with the in vivo hepatic overall intrinsic clearance
, the hepatic uptake clearance in the absence of the albumin by isolated hepatocytes; 
, the in vivo hepatic uptake clearance extrapolated from the in vitro hepatic uptake by isolated hepatocytes; fB, unbound fraction in the blood; 
, the hepatic clearance for the blood; 
, the in vivo hepatic overall intrinsic clearance; 
, the ratio of 
to 
.
| Ligands |  a |  b | fBc | Estimated Parameters by the Facilitated-Dissociation Modeld |  e |  f |  | ||
|---|---|---|---|---|---|---|---|---|---|
 |  | R5% | |||||||
| μl/min per 106 cells | ml/min per kilogram | ml/min per kilogram | ml/min per kilogram | ||||||
| ANS | 54.8 ± 4.5g | 263 ± 22 | 0.00796 | 3.51 ± 1.07h | 24.4 ± 17.5h | 2.70 | 6.43 | 867 | 3.30 |
| PTV | 26.9 ± 6.6 | 83.0 ± 20.3 | 0.00933 | 48.8 ± 11.6h | 199 ± 61h | 10.6 | 9.64 | 1520 | 18.3 |
↵a Data shown in Figs 5–7.
↵b Calculated using the following physiologic scaling factors: 1.2 × 108 cells/g of liver, 40 g liver/kg body weight for rat, 25.7 g liver/kg body weight for human (Davies and Morris, 1993).
↵c Calculated by dividing the unbound fraction in the plasma by the blood-to-plasma concentration ratio (Chung et al., 1990a; Watanabe et al., 2010).
↵d The parameters estimated by the fitting curves in Fig. 8;
, the relative capacity for the interaction of albumin with the surface of hepatocytes; , the dissociation constant of the bound albumin from the surface; R5%, R value in the presence of 5% albumin.↵e Values from the literature (Chung et al., 1990a; Watanabe et al., 2010).
↵f Calculated using a dispersion model as described previously (Roberts and Rowland, 1986; Iwatsubo et al., 1996).
↵g Converted the unit of
to microliters per minute per 106 cells using a scaling factor of 1.1 × 106 cells/mg protein.↵h ± calculated S.D.
