Relative percentage distribution of [14C]semagacestat and radioactive metabolites in pooled 1-, 4-, 9-, and 24-h plasma from healthy male human subjects after a single 140-mg oral dose of [14C]semagacestat dihydrate
A series of minor metabolites (M8, M11, M17, M22, M25, M33, and P2) were also detected in plasma only by LC/MS at trace amount and were below the limit of quantitation by radioactivity.
| Peak | % of Total Radioactivity | Relative AUCa | ||||
|---|---|---|---|---|---|---|
| 1 h | 4 h | 9 h | 24 h | % of Total Radioactivity | % of Parent | |
| Parent | 80.45 | 59.77 | 28.91 | 0.00 | 49.2 | 100 |
| M2 | 3.68 | 15.55 | 41.36 | 79.91 | 27.2 | 55.3 |
| M3 | 6.67 | 9.18 | 9.96 | 20.09 | 9.8 | 19.9 |
| M4 + M5 | 2.47 | 3.57 | 4.70 | 0.00 | 3.3 | 6.8 |
| M6 | 1.70 | 2.00 | 0.00 | 0.00 | 1.0 | 2.1 |
| M7 | 2.10 | 3.71 | 4.84 | 0.00 | 3.3 | 6.7 |
| M19 | 1.04 | 1.33 | 0.00 | 0.00 | 0.7 | 1.4 |
| M20 | 1.24 | 2.00 | 0.00 | 0.00 | 0.9 | 1.9 |
| M21 | 0.00 | 0.00 | 3.60 | 0.00 | 1.3 | 2.5 |
| M30 | 0.00 | 2.90 | 6.64 | 0.00 | 3.1 | 6.4 |
| M32 | 0.64 | 0.00 | 0.00 | 0.00 | 0.2 | 0.4 |
| Total | 100.0 | 100.0 | 100.0 | 100.0 | 100 | N.A. |
N.A., not available.
↵a The AUC0–24 values were calculated using the software Watson (version 7.1; Thermo Scientific, Philadelphia, PA) based on nanogram-equivalents per milliliter values of 1-, 4-, 9-, and 24-h plasma. The nanogram-equivalents per milliliter value for [14C]semagacestat or each metabolite was calculated by multiplying the percentage of total radioactivity value for each compound with nanogram-equivalents per milliliter of the total radioactivity at a given time point. These values are to be considered as semiquantitative only.