Remacemide hydrochloride: a placebo-controlled, one month, double-blind assessment of its safety, tolerability and pharmacokinetics as adjunctive therapy in patients with epilepsy

Forty patients (33 male, 7 female) with refractory epilepsy were randomized to receive ascending weekly doses of adjunctive remacemide hydrochloride i n a b.i.d. or q.i.d. regimen, or placebo for up to 1 month. Assessments inc luded routine physical examination and laboratory tests, recording of adver se events and seizure frequency, and neuropsychological tests. Trough plasm a concentrations of concomitant AEDs were measured at weekly intervals. Tro ugh plasma concentrations of remacemide and its desglycinyl metabolite were measured before each dose increment, and complete 24-hour profiles were me asured at steady state following administration of 600 mg day(-1) and 1200 mg day(-1) A daily dose of 1200 mg was well tolerated in a q.i.d. regimen and up to 80 0 mg was well tolerated in a b.i.d. regimen. The most common adverse events were dizziness, diplopia, dyspepsia and abdominal pain. On some occasions, these were considered to be related to raised concentrations of concomitan t AEDs. No adverse effects were observed on seizure frequency. Neuropsychol ogy tests revealed no significant changes. Remacemide and the desglycinyl m etabolite demonstrated dose proportional pharmacokinetics over the dose ran ge tested. (C) 2000 BEA Trading Ltd.