Distribution of radioactive metabolites in pooled plasma after an oral dose of [14C]apixaban to intact mice, rats, rabbits, dogs, and humans
Human data for subjects without bile collection have been presented previously (Raghavan et al., 2009) and are included here for comparison. The samples at all other time points for rabbit, 12 h for mouse, and 24 and 48 h for all species were not analyzed because of low levels of radioactivity.
Metabolite | Mouse | Rat | Rabbit | Dog | Human | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 h | 4 h | 1 h | 4 h | 12 h | 1 h | 4 h | 1 h | 4 h | 12 h | 1 h | 6 h | 12 h | |||||||||||||
| % | |||||||||||||||||||||||||
| Apixaban | 97.3 | 75.2 | 95.5 | 94.6 | 91.4 | 9.1 | 8.9 | 95.9 | 93.7 | 92.1 | 98.4 | 83.2 | 71.6 | ||||||||||||
| M1 | N.D. | N.D. | N.D. | 0.4 | 0.9 | 23.4 | 4.2 | N.D. | 0.2 | 0.4 | 1.6 | 15.8 | 28.4 | ||||||||||||
| M2 | 0.6 | 3.1 | 0.6 | 0.9 | 1.1 | 29.2 | 17.4 | 1.1 | 2.5 | 2.5 | N.D. | N.D. | N.D. | ||||||||||||
| M4 | N.D. | N.D. | 0.7 | 0.8 | 0.7 | N.D. | N.D. | N.D. | N.D. | N.D. | N.D. | N.D. | N.D. | ||||||||||||
| M7 | 0.4 | 2.8 | 0.3 | 0.4 | 0.4 | N.D. | N.D. | N.D. | N.D. | N.D. | N.D. | 0.75 | N.D. | ||||||||||||
| M10 | N.D. | N.D. | N.D. | N.D. | N.D. | N.D. | N.D. | N.D. | N.D. | N.D. | N.D. | 0.34 | N.D. | ||||||||||||
| M13 | 0.7 | 5.8 | N.D. | N.D. | N.D. | N.D. | N.D. | N.D. | N.D. | N.D. | N.D. | N.D. | N.D. | ||||||||||||
| M14 | 0.4 | 2.4 | N.D. | N.D. | N.D. | 37.7 | 53.3 | N.D. | N.D. | N.D. | N.D. | N.D. | N.D. | ||||||||||||
| Othersa | 0.6 | 10.8 | N.D. | N.D. | N.D. | 1.2 | 16.2 | N.D. | 0.1 | 1.0 | N.D. | N.D. | N.D. | ||||||||||||
| Totalb | 100 | 100 | 97.1 | 97.1 | 94.5 | 100 | 100 | 97.0 | 96.5 | 96.0 | 100 | 100 | 100 | ||||||||||||