Gabapentin in the management of convulsive disorders

Gabapentin, in clinical use since 1993, is indicated as an adjunctive antie pileptic drug (AED) for treatment of complex partial seizures, with or with out secondary generalization, in patients over 12 years of age. Although se veral cellular actions have been described in the literature, the molecular mechanism(s) of action responsible for the anticonvulsant effect of gabape ntin has not been conclusively determined. It is likely that gabapentin has multiple concentration-dependent actions that combine in a unique manner t o produce antiepileptic efficacy. The pharmacokinetic properties of this wa ter-soluble, amino-acid AED are generally favorable. Absorption appears to be dependent on transport by the L-system amino acid transporter. Eliminati on of unmetabolized drug occurs by the renal route. Although its therapeuti c range is not well characterized, gabapentin has a broad therapeutic index . This implies that a wide range of doses can be used, based on individual patient needs, without significant limitation due to dose-dependent side ef fects. Gabapentin has few drug-drug interactions, none of which is clinical ly limiting. Several studies have demonstrated the long-term efficacy of ga bapentin with no systematic evidence of tachyphylaxis. In addition, there i s increasing evidence to support the use of gabapentin as monotherapy. Gaba pentin is safe and is generally well tolerated. To date, nearly 3 million p atients have been treated in studies and in open use without causal relatio nship to a specific life-threatening organ toxicity. Seizure control superi or to that observed in well-controlled trials has been reported at higher d oses used in clinical practice and in studies. Therefore, gabapentin dosing must be optimized on an individual basis to achieve an adequate trial of t he drug and obtain the best seizure control.