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The effects of ethanol on the pharmacokinetics, pharmacodynamics, safety, and tolerability of ezogabine (retigabine).

Abstract：

BACKGROUND:The antiepileptic drug ezogabine (EZG; US adopted name for retigabine [the international nonproprietary name]) reduces neuronal excitability by enhancing potassium channel activity. EZG has been approved as adjunctive treatment for adults with partial-onset seizures. OBJECTIVE:The goal of this study was to examine the impact of coadministration of ethanol 1 g/kg on the safety and tolerability of EZG and the consequences of coadministration on pharmacokinetic (PK) and pharmacodynamic (PD) parameters in healthy volunteers. METHODS:In a randomized, 4-way crossover, partially double-blind study, volunteers received 4 oral treatments (EZG 200 mg + ethanol placebo [light apple juice]; placebo + ethanol 1 g/kg; EZG 200 mg + ethanol 1 g/kg; or placebo + ethanol placebo) separated by 5 to 21 days. RESULTS:PK and PD parameters were evaluated in 17 healthy volunteers (19 to 55 years) who were currently moderate alcohol drinkers. Ethanol coadministration increased EZG AUC(0-∞) and C(max) by 36% and 23%, respectively. EZG had no impact on ethanol PK. Ethanol alone impaired balance, blurred vision, and increased intoxication and dizziness. Objective tests (reaction times, response accuracy, attention, and manual tracking) were also impaired by ethanol. EZG treatment alone had no impact on PD measures other than a variable, transient increase in blurred vision (vision clear-crisp visual analog scale scores). Treatments were generally tolerated, with no serious adverse events or discontinuations owing to adverse events. CONCLUSIONS:Ethanol increased EZG exposure, which did not seem to be clinically relevant. Except for an increase in blurred vision, impairment effects observed were related primarily to ethanol and were not exacerbated by the addition of EZG, which was generally tolerated with or without ethanol.

journal_name

Clin Ther

journal_title

Clinical therapeutics

authors

Crean CS,Tompson DJ

doi

10.1016/j.clinthera.2012.12.003

subject

Has Abstract

pub_date

2013-01-01 00:00:00

pages

87-93

issue

eissn

0149-2918

issn

1879-114X

pii

S0149-2918(12)00669-8

journal_volume

pub_type

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The effects of ethanol on the pharmacokinetics, pharmacodynamics, safety, and tolerability of ezogabine (retigabine).