Ezogabine: a novel antiepileptic as adjunctive therapy for partial onset
seizures.
Author(s): Owen RT.
Affiliation(s): scientific.prousjournals@thomsonreuters.com
Publication date & source: 2010, Drugs Today (Barc). , 46(11):815-22
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.
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