Pharm Res. 1993 Oct;10(10):1442-5.  

Pharmacokinetics, mass balance, and induction potential of a novel GABA uptake
inhibitor, CI-966 HCl, in laboratory animals.

Radulovic LL, Bockbrader HN, Chang T.

Pharmacokinetics/Drug Metabolism Department, Parke-Davis Pharmaceutical Research
Division, Warner-Lamber Company, Ann Arbor, Michigan 48105.

CI-966 exhibits anticonvulsant properties in various animal models. The 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 with a tmax of 0.7 hr. In
rats given 5 mg/kg oral, a mean tmax of 4.0 hr was observed. Following iv
administration of the same respective doses, elimination t1/2 in dogs and rats
averaged 1.2 and 4.5 hr. Absolute oral bioavailability of CI-966 was 100% in
both species. Following oral dosing of [14C]CI-966 HCl to dogs, fecal, and
urinary excretion accounted for 89% and 2.3% of the 14C dose, respectively. In
bile-duct 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 hepatic mixed function
oxidases, as determined by hexobarbital sleeping time.

PMID: 8272405 [PubMed - indexed for MEDLINE]