Safety, tolerability, and pharmacokinetics of remacemide in children

Eleven patients (nine males, two females), 9-14 years of age, received adju nctive therapy with remacemide in an open ascending-dose study at two resid ential centers in the United Kingdom. Children taking enzyme-inducing drugs were given remacemide twice daily, starting at approximately 4 mg/kg per d ay and doubling the dose at two weekly intervals to a target dose of approx imately 16 mg/kg per day. Children not taking enzyme-inducing drugs (n = 5) received half of these doses. After the dose-escalation phase, remacemide was slowly withdrawn over 2 weeks except in two children who, because of ap parent benefit, entered a continuation phase. Remacemide generally was well tolerated in doses up to 13.5 mg/kg per day. Adverse events were similar t o those reported in adults, with central nervous system and gastrointestina l events being the most common, One patient died after a suspected seizure, which was unlikely to have been related to remacemide treatment. No advers e effects on neuropsychologic functioning were observed; effects on vital s igns and laboratory variables were not clinically significant. The pharmaco kinetic profile for remacemide and its desglycinyl metabolite in children i s similar to that seen in adult patients. Plasma concentrations of remacemi de and the desglycinyl metabolite are reduced in the presence of concomitan t antiepileptic drugs with hepatic enzyme-inducing activity. (C) 2001 by El sevier Science Inc, All rights reserved.