Ezogabine: a novel antiepileptic as adjunctive therapy for partial onset seizures

Ezogabine (retigabine) is a novel antiepileptic agent which primarily acts to stabilize neuronal potassium-gated ion channels. Currently no other marketed antiepileptic drugs (AEDs) share this mode of action. Ezogabine's pharmacokinetic profile is characterized by rapid absorption and linear, dose-related kinetics across the therapeutic dose range of 600-1200 mg/day. It is not metabolized by the cytochrome P450 system but by N-glucuronidation and N-acetylation. One acetylated metabolite (AWD-21-360) has some minor pharmacological activity as an anticonvulsant. Drug interactions with other AEDs are minimal. Double-blind, randomized, controlled phase II and III trials using ezogabine 600-1200 mg/day as an adjunctive AED for partial onset seizures demonstrate reduced seizure frequencies of approximately 23-44% across the dose range. Long-term open-label extensions up to 12 months demonstrate median seizure reductions of approximately 50% with no signal for tolerance. The most common adverse events, comprising dizziness, somnolence, headache and fatigue, were dose-related and affected the central nervous system.