Cross-species comparison of excretory routes and metabolite profiles after oral administration of [14C]1
| Recoveryc | Rata | Monkeya | Ratb | Monkeyb | ||||
|---|---|---|---|---|---|---|---|---|
| 89.8 ± 1.9 | 90.5 ± 4.7 | |||||||
| Urine | Feces | Cage Rinse | Urine | Feces | Cage Rinse | Biled | Biled | |
| Dose excretedc | 40.4 ± 6.8 | 31.0 ± 6.3 | 18.5 ± 7.8 | 76.0 ± 5.3 | 1.5 ± 0.4 | 13.0 ± 4.7 | 71.7 ± 7.1 | 5.6 |
| 14C profilede | 87.3 ± 2.8 | 70.2 ± 6.8 | 71.1 ± 5.4 | 89.4 ± 2.2 | N.A. | 85.3 ± 7.8 | 99.8 ± 0.1 | 81.7 |
| Metabolite profilec | ||||||||
| 1 | 22.4 ± 5.4 | 15.5 ± 4.2 | 7.7 ± 4.5 | 3.4 ± 1.5 | N.D. | 1.2 ± 1.2 | 2.2 ± 1.8 | 0.1 |
| M1 | 3.4 ± 2.1 | 1.3 ± 0.7 | 1.7 ± 0.9 | 5.7 ± 1.8 | N.D. | 0.8 ± 0.5 | — | — |
| M2 | 2.9 ± 1.2 | 2.3 ± 0.9 | 1.3 ± 0.4 | 1.9 ± 0.8 | N.D. | 0.5 ± 0.0 | — | — |
| M3/M4f | 5.0 ± 1.8 | 2.6 ± 0.7 | 2.3 ± 0.6 | 14.7 ± 2.1 | N.D. | 2.2 ± 0.9 | — | — |
| M5 | 1.6 ± 0.4 | — | — | 41.9 ± 4.8 | N.D. | 6.9 ± 2.6 | — | 4.4 |
| M6 | — | — | — | — | N.D. | — | 69.4 ± 7.3 | — |
| 2 | — | — | — | — | N.D. | — | — | — |
| 3 | — | — | — | — | N.D. | — | — | — |
| 4 | — | — | — | — | N.D. | — | — | — |
—, not detected; N.A., not applicable; N.D., not determined.
↵a Intact animals (n = 3 rats/gender or n = 2 monkeys/gender).
↵b Bile duct-cannulated animals (n = 2 rats/gender or n = 2 male monkeys).
↵c Percentage of dose.
↵d Sum of dose recovered in bile, urine, and feces from 0–48 h postdose. For rats, no excreta or cage rinse was collected. For monkeys, 66.1, 0.5, and 16.1% of the dose was recovered in urine, feces, and cage rinse, respectively.
↵e For each matrix, this value (%) is calculated by dividing the sum of the metabolite profile by the dose excreted and multiplying by 100.
↵f Metabolites were quantified as one radioactive entity because they were resolved by mass spectrometry but not by radiochromatography.