TABLE 5

In vitro and in vivo intrinsic clearance parameters in rat

The correction factor between in vitro and in vivo values is defined as the factor over and above hepatocellularity (117 and 215 million cells/g liver for rat and dog, respectively).

CompoundΨIntrinsic clearance
In VitroIn Vivo
CLint, passCLint, uptakeCLint, metCLint, L, passCLint, L, uptakeCLint, L
μl · min1 · 106 cells1ml · min1 · kg1
Losartan237.0 ± 2.0190 ± 1.71.5 ± 0.657.726002.3
Ramatroban5.961 ± 44324 ± 6.24.0 ± 1.7320780021
Telmisartan2.2960 ± 4.41200 ± 6309.7 ± 6.255038,00023
AZ12612 ± 2.5310 ± 1200.53 ± 0.4311016,00010
AZ21004.0 ± 0.78420 ± 1600.22 ± 0.242117,0003.8
Mean correction factor0.83 ± 0.676.5 ± 3.01.9 ± 1.7