Pharmacokinetic parameters of OREX-1019
| Rat | Nonhuman Primate | Rabbit | ||||||
|---|---|---|---|---|---|---|---|---|
| i.v. 1 mg/kg | p.o. 3 mg/kg | s.c. 3 mg/kg | i.v. 3 mg/kg | p.o. 30 mg/kg | i.v. 3.6 mg/kg | s.c. 10 mg/kg | s.l. 30 mg/Rabbita | |
| Cmax (ng/ml) | 463 | 3.72 | 584 | 1290 | 31.3 | 1161 | 161 | 78.0 |
| Tmax (hr) | 0 | 0.333 | 0.333 | 0 | 8 | 0 | 4.4 | 1.0 |
| t1/2 (hr) | 2.07 | ND | 3.22 | 4.14 | 7.11 | 4.01 | ND | 4.13 |
| MRTlast (hr) | 1.38 | 1.44 | 2.50 | 2.85 | 7.89 | 3.10 | 8.83 | 4.44 |
| CL (l/hr per kilogram) | 2.90 | NA | NA | 1.03 | NA | 2.69 | NA | NA |
| Vss (l/kg) | 4.30 | NA | NA | 6.42 | NA | 9.65 | NA | NA |
| AUClast (hr × ng/ml) | 350 | 5.88 | 1269 | 2971 | 442 | 1294 | 2114 | 418 |
| AUC∞ (hr × ng/ml) | 355 | ND | 1275 | 2998 | 471 | 1348 | ND | 426 |
| DAUClastb (hr × kg × ng/ml/mg) | 350 | 1.96 | 423 | 990 | 14.7 | 362 | 211 | 45.3 |
| DAUC∞b (hr × kg × ng/ml/mg) | 355 | ND | 425 | 999 | 15.7 | 378 | NDc | 46.2 |
| Bioavailabilityd (%) | NA | ND | 120 | NA | 1.49 | NA | 58.3 | 12.2 |
AUClast, area under the curve, calculated to the last observable time point; AUC∞, area under the curve, extrapolated to infinity; DAUC, dose-normalized AUC; MRTlast, mean residence time, calculated to the last observable time point; ND, not determined; t1/2, half-life; CL, clearance; Vss, apparent volume of distribution at steady state
↵a Thirty milligrams per rabbit (9.17 mg/kg average).
↵b Dose-normalized by dividing the parameter by the nominal dose in milligrams per kilogram.
↵c Not determined because the terminal elimination phase was not observed.
↵d Bioavailability determined by dividing the individual p.o., s.c., or s.l. DAUClast values by the average i.v. DAUClast value.