ISSN:
1573-904X
Keywords:
GABA uptake inhibitor
;
anticonvulsant
;
pharmacokinetics
;
dose proportionality
;
mass balance
;
enzyme induction/ inhibition
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract CI-966 exhibits anticonvulsant properties in various animal models. The drug acts by inhibiting synaptic uptake of γ-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 t max of 4.0 hr was observed. Following iv administration of the same respective doses, elimination t 1/2 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 HC1 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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1018915123542
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