title: Ezogabine: a novel antiepileptic as adjunctive therapy for partial onset seizures.
abstract: 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.
authors.affiliation: scientific.prousjournals@thomsonreuters.com
authors.forename: Richard T
authors.initials: RT
authors.lastname: Owen
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002219:Carbamates / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004828:Epilepsies, Partial / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D010655:Phenylenediamines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D000927:Anticonvulsants; D002219:Carbamates; D010655:Phenylenediamines; C101866:ezogabine