TABLE 1

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




C57BL/6

Abcc2(−/−)

Abcg2(−/−)
Liver mass (g) 1.18±0.02 1.4±0.2 1.2±0.2
Bile flow (μl/min/g liver) 1.0±0.3 0.7±0.1 0.9±0.2
Acetaminophen sulfate
Cliver unbound, ss (nM) 171±32 140±64 222±49
Clbile, ss (μl/min/g liver) 18±5 26±6 2.3±0.2*
Clbasolateral, ss (μl/min/g liver) 289±23 272±63 189±42
Acetaminophen glucuronide
Cliver unbound, ss (nM) 2917±1257 972±548 3628±530
Clbile, ss (μl/min/g liver) 2±1 1.8±0.6 0.29±0.09
Clbasolateral, ss (μl/min/g liver) 175±97 554±313 99±18
4-Methylumbelliferyl sulfate
Cliver unbound, ss (nM) 104±22 55±18* 162±22*
Clbile, ss (μl/min/g liver) 2199±495 4096±254* 2±1*
Clbasolateral, ss (μl/min/g liver) 3669±1888 6272±1964 3296±773
4-Methylumbelliferyl glucuronide
Cliver unbound, ss (nM) 1717±402 1210±547 2824±552*
Clbile, ss (μl/min/g liver) 88±43 59±28 24±1
Clbasolateral, ss (μl/min/g liver) 703±387 1152±892 398±45
Harmol sulfate
Cliver unbound, ss (nM) 399±103 342±79 511±100
Clbile, ss (μl/min/g liver) 1081±417 1211±246 12±1*
Clbasolateral, ss (μl/min/g liver) 562±257 497±152 1254±149*
Harmol glucuronide
Clbile, ss (μl/min/g liver) 315±205 248±157 14±2
Clbasolateral, ss (μl/min/g liver)
219±80
204±95
396±51*
  • * p < 0.05, knockout vs. wild type.