TABLE 1

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.

CompoundSpeciesDoseCLpVdsst1/2AUC(0–∞)
mg/kgml/min/kgl/kghng.h/ml
1Rata1.0 (n = 3)73 ± 131.4 ± 0.50.4 ± 0.2233 ± 37
M1bNANA0.8 ± 0.349.8 ± 11.2
1Dogc1.0 (n = 3)12 ± 3.01.3 ± 0.35.3 ± 0.81450 ± 310
M1bNANA6.3 ± 0.8769 ± 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).