TABLE 1

Kinetic parameters for hepatic intrinsic clearance

Active hepatic uptake and passive diffusion clearances on the sinusoidal membrane, biliary clearance on the canalicular membrane, and metabolic clearance were estimated by both in vitro and in vivo experiments. The details of these estimations are described in the text. Values within parentheses indicate the Km value (micromolar) for each clearance.

RatScaling FactorHuman
In VitroIn VivoIn VitroIn Vivo*
ml/min/g liverml/min/g liver
PSinf2.47a,b (32.8)9.06g3.70.4481.66
PSdif0.192a,b0.192e1e0.09240.0924
PSbile
    ATP-dependent0.0433c0.906d (92.3)210.00737c0.154
    Nonsaturable0.234d0.234f
CLmet,int0.7931.33h1.700
(0.846, 80.3)
  • * Predicted by multiplying the in vitro parameter by the SF.

  • a Yamazaki et al. (1993).

  • b Ishigami et al. (1995).

  • c Calculated using eq. 3 (Niinuma et al. (1999)).

  • d Yamazaki et al. (1997).

  • e Assumed that the SF for PSdif is 1.

  • f Assumed negligible interspecies difference between rat and human.

  • g Calculated using eq. 5.

  • h Calculated using eq. 4.