Pharmacokinetic parameters for taurocholate and rosuvastatin in humans and a comparison of human nonrenal (hepatic) clearance (CLH, vivo) with the biliary clearance in vitro predicted from the uptake clearance in SCHH (CLH, vitro)
| CLH, P | RB | CLH, vivo | fB | CLH,vitro (5 h) | CLH,vitro (96 h) | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| KQG | HH190 | Hu0930 | KQG | HH190 | Hu0930 | |||||
| ml · min−1 · kg−1 | ml · min−1 · kg−1 | ml · min−1 · kg−1 (CLH, vitro/CLH, vivo ratio) | ||||||||
| Taurocholate | 0.6a | 20.7b | 0.4c | 9.50 (0.459) | 8.58 (0.415) | 10.9 (0.529) | 8.66 (0.418) | 10.4 (0.502) | 7.14 (0.345) | |
| Rosuvastatin | 4.83d | 0.6a | 8.06d | 0.18d | 2.65 (0.329) | 2.99 (0.372) | 3.23 (0.401) | 2.74 (0.341) | 2.71 (0.337) | 1.99 (0.247) |
CLH, P, the hepatic clearance in vivo based on the plasma concentration was assessed as the difference between the total plasma clearance and the renal plasma clearance for each compound; RB, ratio of the blood concentration to the plasma concentration of each compound; fB, unbound fraction of each compound in the total blood.
a Blood/plasma concentration ratio of these compounds in humans was assumed to be 0.6.
b Biliary clearance of taurocholate was assumed to be the same as the hepatic blood flow rate.
c There are no data for the blood unbound fraction of taurocholate in humans, so we used the value for rats (Inoue et al., 1985).
d These data were obtained from the interview form of CRESTOR.