Formation of phase I metabolites in the incubations of [14C]irosustat with liver microsomes from rat, dog, monkey, and human (males and females separately) after 120-min incubations
Results are expressed as relative percentage of 14C-labeled metabolites from duplicate incubations. Bold represents main metabolites (which accounted for more than 5% of relative percentage in some species).
| Metabolite | Relative Percentage of Peak Area in Radio-HPLC Profiles | |||||||
|---|---|---|---|---|---|---|---|---|
| Rat | Dog | Monkey | Human | |||||
| Male | Female | Male | Female | Male | Female | Male | Female | |
| P-14 | N.D. | N.D. | 2.1 | 0.5 | 1.3 | 2.3 | N.D. | N.D. |
| M7 | 4.5 | 3.7 | 14.7 | 8.1 | 48.5 | 58.8 | 10.1 | 10.4 |
| M8 | 2.2 | 1.3 | 4.9 | 2.8 | 23.1 | 25.0 | 5.0 | 4.2 |
| M9 | 0.6 | 0.4 | 1.4 | 1.0 | 4.4 | 1.3 | 2.4 | 1.6 |
| M10 | 0.5 | 1.0 | 0.5 | 0.3 | 2.5 | 0.6 | 1.6 | 1.1 |
| M11 | 0.9 | 2.0 | N.D. | N.D. | N.D. | N.D. | 0.7 | 0.9 |
| P-23 | N.D. | N.D. | 0.5 | 0.7 | N.D. | N.D. | 0.3 | 0.4 |
| P-24 | 0.4 | N.D. | 1.0 | 0.7 | 1.8 | 1.1 | 0.4 | 1.0 |
| M13 | 3.8 | 3.7 | 6.5 | 6.1 | 9.9 | 6.9 | 9.5 | 10.9 |
| M14 | 2.9 | 1.6 | 4.6 | 5.5 | 1.1 | N.D. | 2.5 | 2.5 |
| M15 | 2.1 | 1.3 | 1.6 | 1.3 | N.D. | N.D. | 0.4 | 0.8 |
| M16 | 5.4 | 4.2 | 7.2 | 7.4 | 5.0 | 3.3 | 8.1 | 9.1 |
| M18 | 0.5 | 0.4 | 0.7 | 0.5 | —a | —a | 3.2 | 3.3 |
| [14C]Irosustat | 58.7 | 59.2 | 35.5 | 44.8 | 2.4 | 0.7 | 44.6 | 43.3 |
| P-36 | N.D. | 0.6 | 0.9 | 0.7 | N.D. | N.D. | 1.6 | 1.4 |
| 667-Coumarin | 17.4 | 20.8 | 18.0 | 19.6 | —a | —a | 9.8 | 9.3 |
N.D., peak not detected.
↵a —, peak detected in samples corresponding to intermediate incubation periods.