Metabolic pattern in plasma of WT and mdr1a/1b(−/−) mice after intravenous administration of 0.5 mg/kg or oral administration of 0.5 or 4 mg/kg [14C]sorafenib tosylate
n = 3 animals/time point, pooled plasma (50 μl/animal).
| Dose and Time | Component | Percentage of Radioactivity | |||
|---|---|---|---|---|---|
| M-2 | M-3 | M-4 | Sorafenib | ||
| Intravenous (0.5 mg/kg) | |||||
| 0.5 h | WT | 0.37 | 0.43 | 98.1 | |
| 1 h | 1.39 | 98.0 | |||
| 2 h | 0.71 | 1.21 | 97.3 | ||
| 4 h | 1.72 | 3.23 | 95.1 | ||
| 0.5 h | mdr1a/1b(−/−) | 0.55 | 0.14 | 98.5 | |
| 1 h | 0.15 | 0.93 | 0.48 | 97.8 | |
| 2 h | 1.52 | 0.57 | 93.9 | ||
| 4 h | 1.72 | 2.18 | 95.1 | ||
| Oral (0.5 mg/kg) | |||||
| 1 h | WT | ||||
| 4 h | 2.35 | 4.11 | 4.31 | 88.8 | |
| 1 h | mdr1a/1b(−/−) | 1.32 | 1.81 | 0.49 | 94.4 |
| 4 h | 6.21 | 4.67 | 4.34 | 84.8 | |
| Oral (4 mg/kg) | |||||
| 1 h | WT | 2.71 | 2.21 | 0.88 | 93.2 |
| 4 h | 6.32 | 3.77 | 5.29 | 82.9 | |
| 1 h | mdr1a/1b(−/−) | 3.82 | 2.37 | 1.21 | 90.9 |
| 4 h | 8.17 | 3.89 | 4.67 | 81.9 | |