GDC-0425 and its metabolites measured in plasma and excreta following a single oral administration to Sprague-Dawley rats
Plasma are mean results for male and female rats (n = 1 per sex per time point). Urine and feces are mean results for bile duct–intact animals (n = 3 per sex), and bile is the mean results for bile duct–cannulated animals (n = 3 per sex).
| Analyte | Biotransformation | Plasma | Dose Recovered | ||
|---|---|---|---|---|---|
| TRA 0–48 h | Urine | Feces | Bilea | ||
| % | % | % | % | ||
| GDC-0425 | Parent compound | 36.1 | 11.0 | 5.29 | 0.64 |
| M1 | Thiocyanate | 37.0 | 0.06 | 0.31 | 0.08 |
| M2 | Glucuronidation | ND | 1.31 | 0.87 | 2.11 |
| M3 | O-dealkylation+glucuronidation | ND | 1.31 | ND | D |
| M4 | N-deethylation+hydroxylation+glucuronidation | ND | ND | ND | 2.33 |
| M5 | O-dealkylation | D | 3.61 | 2.34 | 0.49 |
| M6 | Hydroxylation+glucuronidation | D | 0.53 | ND | 10.6 |
| M7 | N-deethylation+hydroxylation | ND | 0.41 | 5.00 | 1.29 |
| M9 | Hydroxylation | D | 1.81 | 22.9 | 5.28 |
| M10 | N-deethylation | 3.17 | 9.74 | 11.6 | 1.82 |
| M14 | Hydroxylation | D | 1.71 | D | 1.82 |
| M16 | Oxidation (+14 Da) | 9.00 | 0.78 | 2.64 | 0.14 |
| % Dose | N/A | 32.7 | 59.1 | 30.9a | |
D, detected by mass spectrometry; N/A, not assessed; ND, not detected; TRA, total radioactivity.
↵a Bile was collected from bile duct-cannulated animals that were separate from the animals described for urine and feces.