Table 3.
Profile of enflicoxib metabolites in cryopreserved hepatocytes from rats and dogs.
| Metabolite | Time (min) | LC-MS Peak Area | Metabolism Rate pmol (min·106 cells)-1 |
||||
|---|---|---|---|---|---|---|---|
| Substrate: Enflicoxib | Substrate: E-6132 | ||||||
| Wistar Rat | Beagle Dog | Wistar Rat | Beagle Dog | Rat | Dog | ||
| Unchanged enflicoxib | 0 | 1368 (20) | 1377 (20) | 0 | 0 | 88.5* | - |
| 120 | 642 (9.4) | 1415 (20.5) | 0 | 0 | 15.7* | ||
| 180 | 492 (7.2) | 1182 (17.2) | 0 | 0 | |||
| M7 | 0 | 0 | 0 | 0 | 0 | - | - |
| 120 | 2 | 0 | 0 | 0 | - | - | |
| 180 | 1 | 1 | 0 | 0 | - | - | |
| M8 | 0 | 0 | 0 | 0 | 0 | - | - |
| 120 | 1445 | 196 | 0 | 0 | - | - | |
| 180 | 1411 | 266 | 0 | 0 | - | - | |
| E-6132 | 0 | 0 | 0 | 16180 (20) | 18247 (20) | - | - |
| 120 | 2030 | 58 | 16575 (20.5) | 17449 (19.1) | 23.4† | nd | |
| 180 | 2171 | 77 | 12771 (15.8) | 18883 (20.7) | - | - | |
| M7 Sulfate | 0 | 0 | 0 | 0 | 0 | - | - |
| 120 | 9 | 0 | 0 | 0 | - | - | |
| 180 | 11 | 0 | 0 | 0 | - | - | |
| M7 Glucuronide | 0 | 0 | 0 | 0 | 0 | - | - |
| 120 | 9 | 0 | 0 | 0 | - | - | |
| 180 | 11 | 0 | 0 | 0 | - | - | |
| M8 Glucuronide | 0 | 0 | 0 | 0 | 0 | - | - |
| 120 | 109 | < 1 | 0 | 0 | - | - | |
| 180 | 154 | < 1 | 0 | 0 | - | - | |
| E-6132 Glucuronide | 0 | 0 | 0 | 0 | 0 | - | - |
| 120 | 7 | 0 | 141 | 1 | - | - | |
| 180 | 13 | 0 | 170 | 1 | - | - | |
| Enflicoxib Glucuronide | 0 | 0 | 0 | 0 | 0 | - | - |
| 120 | 119 | 1 | 0 | 0 | - | - | |
| 180 | 131 | 1 | 0 | 0 | - | - | |
nd not determined
* transformation rate calculated for the time range 0-120 minutes
† transformation rate calculated for the time range 0-180 minutes In parentheses concentration of substrate remaining (µM)