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.