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 in a b.i.d. or q.i.d. regimen, or placebo for up to 1 month. Assessments included routine physical examination and laboratory tests, recording of adverse events and seizure frequency, and neuropsychological tests. Trough plasma concentrations of concomitant AEDs were measured at weekly intervals. Trough plasma concentrations of remacemide and its desglycinyl metabolite were measured before each dose increment, and complete 24-hour profiles were measured 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 800 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 concomitant AEDs. No adverse effects were observed on seizure frequency. Neuropsychology tests revealed no significant changes. Remacemide and the desglycinyl metabolite demonstrated dose proportional pharmacokinetics over the dose range tested.