Metabolism of [14C]bicifadine by mouse, rat, monkey, and human hepatic hepatocytes
Isolated hepatocytes (0.75 × 106 cells/ml) were incubated with 10 μM [14C]bicifadine with an atmosphere of 5% CO2 at 37°C for 60 and 180 min as described under Materials and Methods. The formation of the products was measured using HPLC with radioflow detection.
Species | Time | M1 | M2 | M3 | M4 | M5 | M6 | M7 | M8 | M9/M10a | Bicifadinea | M11 | M12 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| min | |||||||||||||
| Mouse | 0 | N.D. | N.D. | N.D. | N.D. | N.D. | N.D. | N.D. | N.D. | N.D. | 96.6 | N.D. | N.D. |
| 60 | 0.34 | 6.6 | 10.5 | N.D. | N.D. | N.D. | N.D. | 2.7 | M9 7.3 | 22.7 | 4.4 | 44.2 | |
| 180 | 1.2 | 1.2 | 25.0 | N.D. | N.D. | N.D. | N.D. | 0.5 | M9 35.9 | 9.9 | 5.9 | 16.7 | |
| Rat | 0 | N.D. | 0.6 | 0.7 | N.D. | N.D. | N.D. | N.D. | N.D. | N.D. | 91.1 | N.D. | N.D. |
| 60 | Y | 2.5 | 7.8 | N.D. | Y | Y | N.D. | N.D. | M10 2.3 | 44.8 | 3.8 | 30.5 | |
| 180 | Y | 1.2 | 13.3 | N.D. | 1.2 | Y | N.D. | N.D. | M9/10 4.2 | 13.2 | 4.7 | 56.2 | |
| Monkey | 0 | N.D. | N.D. | N.D. | N.D. | N.D. | N.D. | N.D. | N.D. | N.D. | 95.9 | N.D. | N.D. |
| 60 | 0.4 | 29.0 | 14.1 | 1.9 | N.D. | N.D. | 1.2 | 20.1 | M9 8.9 | 6.3 | 1.3 | 17.9 | |
| 180 | 1.6 | 17.9 | 24.4 | 1.9 | N.D. | N.D. | 5.9 | 8.5 | M9 29.5 | 3.6 | 1.5 | Y | |
| Human | 0 | N.D. | N.D. | N.D. | N.D. | N.D. | N.D. | N.D. | N.D. | N.D. | 96.7 | N.D. | N.D. |
| 60 | Y | 2.7 | 5.9 | N.D. | Y | Y | N.D. | N.D. | M10 5.1 | 26.8 | 2.7 | 55.6 | |
|
| 180 | Y | 1.5 | 13.2 | N.D. | Y | Y | N.D. | N.D. | M10 7.8 | 6.5 | 2.5 | 66.4 |
N.D., not detected; Y, detected by LC/MS/MS but <0.3% of profiled radioactivity.
↵ a Percentages of bicifadine, M9, and M10 at 60 and 180 min derived from LC/MS/MS sample runs.