Cross-species pharmacokinetics summary for 1 and total radioactivity after oral administration of [14C]1
| 1a | Total Radioactivity | |||
|---|---|---|---|---|
| Rat | Monkey | Rat | Monkey | |
| Tmaxb | 2.1 ± 2.4 | 1.0 ± 0.0 | 4.8 ± 2.6 | 1.0 ± 0.0 |
| Cmaxc | 116 ± 37 | 96.2 ± 21.6 | 183 ± 29 | 580 ± 146 |
| t1/2b | 9.8 ± 1.8 | 4.7 ± 0.9 | 18.9 ± 5.7 | 5.3 ± 1.0 |
| AUC0–24d | 1609 ± 507 | 726 ± 195 | 3303 ± 352 | 3188 ± 156 |
| AUC0-∞d | 2042 ± 497 | 769 ± 204 | 5702 ± 996 | 3359 ± 140 |
| CL/Fe | 25.3 ± 5.1 | 33.8 ± 7.7 | N.A. | N.A. |
| CLRef | 5.6 ± 1.2 | 1.1 ± 0.6 | N.A. | N.A. |
| (CLR/fu)/GFRg | 2.2 ± 0.5 | 0.6 ± 0.3 | N.A. | N.A. |
N.A., not applicable.
↵a Oral doses of 3 and 1.5 mg/kg [14C]1 for rats and monkeys, respectively.
↵b Units are hours.
↵c Units are ng/ml and ng-Eq/ml for 1 and total radioactivity, respectively.
↵d Units are ng · h/ml and ng-Eq · h/ml for 1 and total radioactivity, respectively.
↵e Units are ml/min/kg.
↵f Calculated by Ae0-t/AUC0-∞ and animal weight-normalized; t = 72 and 48 h for rat and monkey, respectively.
↵g Unbound plasma fraction (fu) was 0.43 and 0.52 for rat and monkey, respectively. Glomerular filtration rate was assumed to be 1.31 ml/min in rats and 10.4 ml/min in monkeys (Davies and Morris, 1993) and animal weight-normalized.