Mean pharmacokinetic parameters of compound 1 and cyclic ether metabolite M1 in after intravenous (1 mg/kg) administration of compound 1 to Wistar-Han rats and beagle dogs
Pharmacokinetic parameters are expressed as mean ± S.D.
| Compound | Species | Dose | CLp | Vdss | t1/2 | AUC(0–∞) |
|---|---|---|---|---|---|---|
| mg/kg | ml/min/kg | l/kg | h | ng.h/ml | ||
| 1 | Rata | 1.0 (n = 3) | 73 ± 13 | 1.4 ± 0.5 | 0.4 ± 0.2 | 233 ± 37 |
| M1b | NA | NA | 0.8 ± 0.3 | 49.8 ± 11.2 | ||
| 1 | Dogc | 1.0 (n = 3) | 12 ± 3.0 | 1.3 ± 0.3 | 5.3 ± 0.8 | 1450 ± 310 |
| M1b | NA | NA | 6.3 ± 0.8 | 769 ± 136 |
NA, not applicable.
↵a Intravenous administration of compound 1 in 5% DMSO/95% of 30% 2-hydroxypropyl-β-cyclodextrin.
↵b Concentrations of M1were estimated in animals that were administered compound 1 by i.v. route.
↵c Intravenous administration of compound 1 as a solution in 25% 2-hydroxypropyl-β-cyclodextrin/Tris buffer (100 mM) (pH = 8.0).