GABAPENTIN

The amino acid antiepileptic drug (AED) gabapentin (GBP) is indicated for adjunctive use in the treatment of partial seizures with or withou t becoming secondarily generalized in individuals older than 12 years. GBP was about as potent as phenytoin in the maximal electroshock test , but had a different profile of efficacy than standard antiepileptics in a range of animal models. Possible mechanisms of action include bi ochemical effects enhancing the ratio of gamma-aminobutyric acid (GABA ) to glutamate, ion-channel actions (direct or indirect), and/or or en hancement of nonsynaptic GABA release. The anticonvulsant effect appea rs to depend on concentration of gabapentin in neurons, presumably by the L-system amino acid transporter that has been implicated in absorp tion from the gut. Data from studies for U.S. Food and Drug Administra tion (FDA) approval suggested a direct relationship of clinical respon se to dose and efficacy did not plateau at the doses used. The maximal ly effective dose, relationship of efficacy to blood level, and maximu m tolerable dose are not yet known conclusively. Lack of significant b inding to plasma proteins and lack of liver metabolism contribute to t he absence of known limiting drug-drug interactions, particularly with other AEDs. Excretion intact in the urine affords dose adjustment on the basis of creatinine clearance. A half-life of approximately 7 h ne cessitates multiple doses daily for many individuals. The medication i s well tolerated, in general. Side effects tend to be mild to moderate in intensity, most frequently affect the central nervous system, and resolve with time in many individuals. GBP has been prescribed for app roximately 70,000 individuals worldwide without untoward incidence of severe systemic toxicity to date. Safety data continue to accumulate. GBP has been labeled category C on the basis of effects on rodent fetu ses. Experience with use in pregnant women is limited and human terato genic effects have not been reported. Data from ongoing monotherapy tr ials will help to clarify the range of clinical utility of gabapentin.