Distribution of radioactivity in plasma
[14C]-1 was administered by mouth as a single dose to intact animals (mice, rats, monkeys) and to BDC animals (dogs), and plasma was collected at selected time points over 8 hours. Samples were processed as described in Materials and Methods and analyzed by LC-MS/MS with fraction collection and offline scintillation counting. Data is expressed as a percentage of the radioactivity in each sample. The sum of radioactivity reported in some columns is less than the total radioactivity, reflecting the presence of minor metabolites that were not identified.
| Mouse | Rat | BDC Dog | Monkey | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 h | 4 h | 1 h | 2 h | 4 h | 1.5 h | 4 h | 8 h | 1 h | 4 h | 8 h | |
| 1 | 89.8 | 74.6 | 84.6 | 85.2 | 88.2 | 87.5 | 92.4 | 93.9 | 78.2 | 74.2 | 85.6 |
| 3 | 1.6 | 4.0 | 2.9 | 2.8 | 2.6 | ms | ms | ms | 21.8 | 17.8 | 14.4 |
| 4 | 3.2 | 2.1 | 2.0 | 3.0 | 1.9 | ms | 2.3 | 2.0 | — | — | — |
| 5 | 1.5a | 3.0a | — | — | — | ms | 1.2a | 0.6a | — | — | — |
| 26 | 4.5 | 4.0 | 3.5 | ms | — | — | — | ||||
| 7 | 2.8 | 6.7 | — | — | — | — | — | — | — | — | — |
| 8 | — | — | 1.5 | 2.0 | 1.5 | — | — | — | — | — | — |
| 9 | ms | 1.5 | 0.3 | 0.7 | 0.7 | 2.9 | ms | ms | — | — | — |
| 10 | ms | 2.4 | — | — | — | — | — | — | — | — | — |
| 12 | — | — | — | — | — | — | — | — | ms | 2.1 | ms |
| Sum | 98.9 | 94.3 | 95.8 | 97.7 | 98.4 | 90.4 | 95.9 | 96.5 | 100.0 | 94.1 | 100.0 |
—, not detected; ms, detected by mass spectrometry only.
↵a Compounds 5 and 26 coeluted during HPLC. Entries represent the sum of radioactivity attributed to these two metabolites.