TABLE 2

In vitro clearance (CL)int (mean ± S.D., n = 3 for HepaRG and PHH, n = 4 for HµREL), predicted in vivo CLint (fold difference between predicted and observed in parentheses) and observed in vivo CLint

CompoundsIn vitro CLintPredicted In Vivo CLintObserved In Vivo CLint
Suspended hepatocytesHepaRGPHHHµRELHepaRGPHHHµREL
µl/min/106 cellsml/min/kgml/min/kg
S-warfarinnv0.21bnv0.71 ± 0.30.2 (3.3)nv0.4 (6.7)0.06
Diazepamnv0.40b0.79 ± 0.31.35 ± 0.090.5 (1.0)0.8 (1.6)1.2 (2.4)0.5
Disopyramidenv0.16a0.21a0.40 ± 0.20.7 (−1.3)0.9 (1.0)1.5 (1.7)0.9
Theophyllinenvnvnvnvnvnvnv1.4
Metoprololnv0.57b2.2 ± 0.70.78 ± 0.156.3 (−5.9)12.3 (−3.0)8.0 (−4.6)37.1
AZ01nv0.30 ± 0.20.93 ± 0.21.40 ± 0.2nv
AZ02nv0.45 ± 0.21.2 ± 0.23.26 ± 0.30.5 (−9.4)1.1 (-4.3)2.3 (−2.0)4.7
Ketoprofen6.6 ± 0.3nv3.9b4.3anv7.5 (3.1)8.1 (3.4)2.4
Sildenafil9.7 ± 0.95.3a7.0 ± 2.06.2 ± 1.76.4 (−1.3)7.9 (−1.1)7.2 (−1.2)8.6
Carvedilol38.1 ± 7.08.6a26.3 ± 3.334.2 ± 2.46.7 (−2.3)15.6 (1.0)19.0 (1.2)15.4
Imipramine4.7 ± 1.1nv8.6 ± 3.11.7 ± 0.06nv50.9 (1.2)15.3 (−2.7)41.5
Ketanserin33.1 ± 3.60.65a8.3 ± 5.814.1 ± 0.51.5 (−6.7)10.2 (1.0)15.3 (1.5)10.1
  • nv, no value.

  • a n = 1.

  • b n = 2.