PHARMACOKINETICS, MASS-BALANCE, AND INDUCTION POTENTIAL OF A NOVEL GABA UPTAKE INHIBITOR, CI-966 HCL, IN LABORATORY-ANIMALS

CI-966 exhibits anticonvulsant properties in various animal models. Th e drug acts by inhibiting synaptic uptake of gamma-aminobutyric acid ( GABA). Oral absorption of CI-966 in dogs given 1.39 mg/kg is rapid wit h a t(max) of 0.7 hr. In rats given 5 mg/kg oral, a mean t(max) of 4.0 hr was observed. Following iv administration of the same respective d oses, elimination t1/2 in dogs and rats averaged 1.2 and 4.5 hr. Absol ute oral bioavailability of CI-966 was 100% in both species. Following oral dosing of [C-14]CI-966 HCl to dogs, fecal, and urinary excretion accounted for 89% and 2.3% of the C-14 dose, respectively. In bile-du ct cannulated rats, biliary excretion is the major elimination pathway of radioactivity (75%). Urinary and fecal excretion accounted for 4.1 and 12%, respectively. CI-966 does not induce or inhibit mouse hepati c mixed function oxidases, as determined by hexobarbital sleeping time .