Vigabatrin.

Abstract

To introduce the reader to the use of a new agent, vigabatrin, in the treatment of refractory complex partial seizures. Clinical trials and pharmacokinetic data are reviewed, as well as neuropathology, adverse effects, drug interactions, and dosage guidelines. A MEDLINE search through March 1992 was used to identify pertinent English-language literature, including clinical trials, reviews, abstracts, and conference proceedings. Indexing terms included vigabatrin and anticonvulsants. All clinical trials (total of 21) were reviewed, as were all pharmacokinetic studies (total of 8). Selected studies highlighting chemistry, pharmacology, neuropathology, and adverse effects were also reviewed. Performed subjectively by the author. Trials were assessed by design, sample size, types of seizures of the subjects, and clinical response. Vigabatrin represents the first of a new class of antiepileptic drugs (AEDs)--the gamma-aminobutyric acid transaminase (GABA-T) inhibitors. Vigabatrin works by selective, irreversible inhibition of GABA-T, thus preventing the breakdown of GABA. It has been shown to produce dose-dependent increases in cerebrospinal fluid GABA concentrations, and decreases in GABA-T activity. Vigabatrin may also cause a decrease in excitation-related amino acids. It is well absorbed, is not protein bound, and is eliminated by glomerular filtration. However, even with a short half-life (5-7 h), vigabatrin may be given once or twice daily because of its mechanism of action. Few drug interactions have been reported with this agent, although decreases in phenytoin concentration may reach clinical significance. Concern over neuropathologic findings (microvacuolization of white matter) in animals caused trials of vigabatrin to be halted in 1983, but trials have now resumed as there is no evidence of toxicity in humans. Clinical efficacy of vigabatrin has been evaluated in controlled trials and appears to be most effective in complex partial seizures, producing a 50 percent or greater reduction in seizure frequency in approximately 50 percent of the adult patients studied. Efficacy in children with partial seizures also appears promising, and one uncontrolled study suggests that further study of vigabatrin in infantile spasms may be warranted. Vigabatrin appears to be effective in treating refractory complex partial seizures in adults and refractory partial seizures in children. Its relatively benign adverse-effect profile and few known drug interactions may given this agent an advantage over existing anticonvulsants. However, definitive conclusions about the role of vigabatrin in epilepsy treatment should await the completion of ongoing Phase II and Phase III trials.