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.