Therapeutic advances in chronic disease · 2011
Retigabine (ezogabine) as add-on therapy for partial-onset seizures: an update for clinicians.
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Harris Jacklyn A, Murphy Julie A
Аннотация
OBJECTIVE: The present study reviewed the pharmacology, pharmacokinetics, efficacy, and safety of retigabine (ezogabine), a potential agent for use as adjunctive treatment in refractory partial-onset seizures.
METHODS: A MEDLINE search (1966-May 2011) was conducted using the key words retigabine, ezogabine, D-23129, epilepsy, and anticonvulsant. Bibliographies of all articles retrieved were also reviewed. All studies including humans and published in English with data describing retigabine for the adjunctive treatment of partial-onset seizures were reviewed.
RESULTS: Retigabine has been shown to interact with the KCNQ2/KCNQ3 subunits of the potassium channels, GABA(A) receptors, and weakly block sodium and calcium channels. Retigabine is 50-60% bioavailable, metabolized by N-glucuronidation and N-acetylation, 80% protein bound, and has few drug-drug interactions. Recent data suggest that retigabine may have a role as adjunctive treatment for refractory partial-onset seizures. Placebo-controlled trials demonstrated a 23.4-44.3% reduction in seizure frequency with 50% responder rates ranging from 23.2% to 47.0% with varying doses of retigabine. The most common adverse effects, occurring in greater than 10% of subjects in the clinical trials, include abnormal gait, confusion, dizziness, fatigue, headache, nausea, somnolence, speech disorder, tremor, urinary tract infection, and blurred vision.
CONCLUSIONS: Retigabine is a promising agent for adjunctive treatment of refractory partial-onset seizures.
METHODS: A MEDLINE search (1966-May 2011) was conducted using the key words retigabine, ezogabine, D-23129, epilepsy, and anticonvulsant. Bibliographies of all articles retrieved were also reviewed. All studies including humans and published in English with data describing retigabine for the adjunctive treatment of partial-onset seizures were reviewed.
RESULTS: Retigabine has been shown to interact with the KCNQ2/KCNQ3 subunits of the potassium channels, GABA(A) receptors, and weakly block sodium and calcium channels. Retigabine is 50-60% bioavailable, metabolized by N-glucuronidation and N-acetylation, 80% protein bound, and has few drug-drug interactions. Recent data suggest that retigabine may have a role as adjunctive treatment for refractory partial-onset seizures. Placebo-controlled trials demonstrated a 23.4-44.3% reduction in seizure frequency with 50% responder rates ranging from 23.2% to 47.0% with varying doses of retigabine. The most common adverse effects, occurring in greater than 10% of subjects in the clinical trials, include abnormal gait, confusion, dizziness, fatigue, headache, nausea, somnolence, speech disorder, tremor, urinary tract infection, and blurred vision.
CONCLUSIONS: Retigabine is a promising agent for adjunctive treatment of refractory partial-onset seizures.