Relative distribution of metabolites in pooled urine, feces, and bile after oral administration of [14C]GDC-0449 to rats and dogs
The percentage of the dose was calculated as the percentage of the sample multiplied by the percentage of excretion from n = 2 for dogs and n = 3 for rats.
| Analyte | Percentage of Dose in Rats | Percentage of Dose in Dogs | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Urine (0–24 h) | Feces (0–48 h) | Bile (0–24 h) | Urine (0–192 h) | Feces (0–144 h) | Bile (0–240 h): M | |||||||||||
| M | F | Mean | M | F | Mean | M | F | Mean | M | F | Mean | M | F | Mean | ||
| GDC-0449 | D | D | D | 44.7 | 40.2 | 42.5 | 0.3 | 0.5 | 0.4 | 0.4 | 0.2 | 0.3 | 23 | 13.2 | 18.1 | 3.8 |
| M1 | D | D | D | D | D | D | D | D | D | —a | — | — | 3.2 | 5.6 | 4.4 | — |
| M3 | 0.4 | 0.1 | 0.3 | 15.9 | 10.2 | 13.1 | 6.6 | 5.6 | 6.1 | 0.3 | 0.3 | 0.3 | 18.9 | 28 | 23.5 | 1.3 |
| M4 | 0.2 | D | 0.2 | — | — | — | 2.5 | 0.5 | 1.5 | 0.3 | 0.7 | 0.5 | — | — | — | 2.4 |
| M5 | D | 0.3 | 0.3 | — | — | — | 5.6 | 8.9 | 7.3 | 0.2 | 0.5 | 0.4 | — | — | — | 3.8 |
| M6 | — | — | — | — | — | — | D | D | D | — | — | — | — | — | — | D |
| M7 | — | — | — | — | — | — | 0.3 | 0.4 | 0.4 | — | — | — | — | — | — | — |
| M8 | — | — | — | — | — | — | 0.2 | 0.2 | 0.2 | — | — | — | — | — | — | — |
| M9 | 0.3 | 1.1 | 0.7 | 1.7 | 5.7 | 3.7 | Db | Db | D | — | — | — | — | — | — | — |
| M10 | 0.4 | 0.3 | 0.4 | — | — | — | — | — | — | 0.2 | 0.3 | 0.3 | — | — | — | — |
| M11 | D | D | D | D | D | D | 0.8 | 0.6 | 0.7 | — | — | — | — | — | — | — |
| M12 | — | — | — | — | — | — | — | — | — | 0.3 | 0.7 | 0.5 | — | — | — | — |
| M13 | D | D | D | D | D | D | D | D | D | 0.3 | 0.2 | 0.3 | 7.1 | 12.1 | 9.6 | 3.1 |
| M14 | 0.5 | D | 0.5 | 0.4 | 0.8 | 0.6 | 0.8 | 0.9 | 0.9 | 0.6 | 1.2 | 0.9 | — | — | — | 1.6 |
| M15 | — | — | — | — | — | — | — | — | — | — | — | — | 3.1 | 4.3 | 3.7 | 0.7 |
| M16 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | 1.6 |
| M17 | D | D | D | — | — | — | 12.7 | 7.0b | 9.9 | — | — | — | — | — | — | — |
| M18 | D | D | D | D | D | D | D | D | D | D | D | D | 3.3 | 5.6 | 4.5 | 1.0 |
| Total dose identifiedc | 1.7 | 1.8 | 1.8 | 62.7 | 56.9 | 59.8 | 29.7 | 24.5 | 27.1 | 2.6 | 4.1 | 3.4 | 58.6 | 68.8 | 63.7 | 19.3 |
| Total dose pooledd | 2.2 | 2.3 | 2.3 | 88.0 | 90.7 | 90.7 | 38.1 | 35.3 | 36.7 | 3.5 | 5.7 | 4.6 | 62.9 | 79.9 | 71.4 | 21.2 |
M, male; F, female; D, detected by LC-MS/MS and radiochromatographic peak was not discernible.
↵a —, not detected.
↵b This metabolite coeluted with M9.
↵c These figures represent the total percentage of the dose of the listed metabolites; the remainder of the radioactivity was distributed in various minor peaks (each representing <5% of the dose) throughout the radiochromatogram. These minimal peaks were not characterized.
↵d These data represent the total percentage of the dose excreted in each route over the time period of sample pooled.