TABLE 2

Steady-state hepatic unbound concentrations and excretory unbound intrinsic clearances (mean ± S.D., n = 3-4/group) of sulfate and glucuronide conjugates formed in the liver from the respective parent compounds




FVB

Abcb1a(−/−)/Abcb1b(−/−)
Liver mass (g) 1.3±0.2 1.34±0.08
Bile flow (μl/min/g liver) 0.9±0.2 1.14±0.06
Acetaminophen sulfate
Cliver unbound, ss (nM) 294±183 234±78
Clbile, ss (μl/min/g liver) 19±10 29±6
Clbasolateral, ss (μl/min/g liver) 388±239 388±102
Acetaminophen glucuronide
Cliver unbound, ss (nM) 971±352 1025±362
Clbile, ss (μl/min/g liver) 2±1 2.8±0.6
Clbasolateral, ss (μl/min/g liver) 545±370 467±133
4-Methylumbelliferyl sulfate
Cliver unbound, ss (nM) 77±39 56±13
Clbile, ss (μl/min/g liver) 4631±2134 5449±758
Clbasolateral, ss (μl/min/g liver) 8309±3857 10216±1795
4-Methylumbelliferyl glucuronide
Cliver unbound, ss (nM) 1989±675 1213±244
Clbile, ss (μl/min/g liver) 37±20 66±20
Clbasolateral, ss (μl/min/g liver) 683±414 1096±391
Harmol sulfate
Cliver unbound, ss (nM) 433±88 317±83
Clbile, ss (μl/min/g liver) 1164±114 1609±240*
Clbasolateral, ss (μl/min/g liver) 702±38 796±200
Harmol glucuronide
Clbile, ss (μl/min/g liver) 138±57 126±35
Clbasolateral, ss (μl/min/g liver)
252±157
178±91
  • * p < 0.05, knockout vs. wild type.