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Gabapentin, an analog of gamma-aminobutyric acid, exhibits anticonvulsant
properties in both animal models and humans. Gabapentin pharmacokinetics was
studied in laboratory animals using HPLC and radiometry. Oral bioavailability
was 40% in monkeys administered 25 mg/kg, 79% in mice and rats receiving 50
mg/kg, and 80% in dogs administered 50 mg/kg. Binding to plasma proteins was <
3%. Maximum blood or plasma concentrations generally occurred within 2 hr of an
oral dose. In rats and monkeys, increases in maximum plasma concentrations
and/or areas under the curve were less than dose-proportional following oral
administration, most likely because of saturable absorption. However,
intravenous pharmacokinetics in rats were linear over the dosage range of 4-500
mg/kg. Mean intravenous elimination half-life was 1.7 hr in rats, 2.9 hr (14C
only) in dogs, and 3.0 hr in monkeys. In rats and dogs, repeated administration
did not alter gabapentin or 14C pharmacokinetics. Additionally, gabapentin did
not induce hepatic cytochrome P450 monooxygenases in rats. There were no age-
(rats only) or gender-associated changes in pharmacokinetic parameters.
[14C]Gabapentin was extensively distributed to tissues. In the dog, gabapentin
was metabolized to N-methylgabapentin (approximately 34% of dose); whereas
metabolism in mouse, rat, and monkey was minimal (< 5%). The principal route of
excretion was via urine. In summary, as an antiepileptic drug, gabapentin
exhibited desirable pharmacokinetic properties, such as linear elimination
kinetics, not highly bound to plasma proteins, not extensively metabolized, and
not an inducer of hepatic cytochrome P450.
PMID: 7600909 [PubMed - indexed for MEDLINE]
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