Lack of pharmacokinetic interaction between remacemide hydrochloride and sodium valproate in epileptic patients

Abstract

A randomized, double-blind, placebo-controlled cross-over study of adjuvant treatment with remacemide hydrochloride was carried out in 17 patients taking sodium valproate (VPA) as monotherapy. Plasma concentration profiles of VPA, remacemide, and its active desglycinyl metabolite (ARL12495XX) were determined following single (300 mg) and multiple dosing (150 or 300 mg twice daily) of remacemide hydrochloride for 14 days with a 300-mg final dose. Central nervous system side-effects were more common at the higher dose, which prompted dosage reduction to 150 mg twice daily for subsequent patients partway through the study. The mean area under the concentration-time curve, peak concentration and pre-dose concentration of VPA were unchanged by remacemide hydrochloride in three patients on the higher and in 10 patients on the lower dose of remacemide. The pharmacokinetic parameters of remacemide and its active metabolite in the VPA-treated patients were similar to those described previously in healthy volunteers. Thus, remacemide hydrochloride does not interfere with the pharmacokinetics of VPA and vice versa.

Remacemide hydrochloride as an add-on therapy in epilepsy: a randomized, placebo-controlled trial of three dose levels (300, 600 and 800 mg / day) in a B.I.D. regimen

“…regimen, as adjunctive therapy in refractory patients with epilepsy receiving hepatic enzyme inducing AEDs. Early studies have shown that plasma concentrations of remacemide and the desglycinyl metabolite are reduced in the presence of hepatic enzyme-inducing drugs such as carbamazepine (CBZ) and phenytoin (PHT) 2,3 . In turn, interaction studies have shown that remacemide increases plasma concentrations of CBZ 3 and PHT 4 by inhibiting their metabolism.…”