Abstracts

Rationale: Rufinamide (RUF) is a recently approved antiepileptic drug (AED) used mainly in refractory epilepsy in children. The knowledge is limited concerning its pharmacokinetics as well as its efficacy in different types of epilepsy. We retrospectively evaluated the dose-related plasma concentrations and efficacy in the first 39 children treated with RUF in our clinic. Methods: The cohort of 39 children, 21 boys and 18 girls, had a mean age of 9.7 years. Their epilepsy onset was at a mean of 1.8 years. Generalized epilepsy was found in 28 and partial in 11. The etiology was heterogeneous. All had pharmacoresistant epilepsy. Clinical efficacy was categorized as >50% seizure reduction, 0-50% seizure reduction, no change or worsening. As a measure of RUF apparent oral clearance, we used the RUF dose-to-concentration ratio which was calculated as: total RUF dose/kg body weight / RUF plasma concentration at steady state. The unit used was (L/[kg/day]). The RUF clearance was related to age and comedication. Results: A >50% seizure reduction was found in 20.5% (8/39) in the study cohort and in 18% (2/11) in those with Lennox-Gastaut syndrome. No correlation was found between age, gender, type of epilepsy or seizures and seizure response. In the study group, the RUF mean dose was 19.8 mg/kg/d (range 10-39) and the mean plasma level was 28 ?mol/L (range 7.2-83). RUF clearance was higher in younger children and the clearance changed significantly in relation to age (p=0.026; regression analysis). Enzyme-inducing AEDs seemed to induce RUF clearance only to a minor degree (6.7%). Children on valproate had a lower RUF clearance than those not on valproate. In younger children (<10 years), RUF clearance was 41% lower if combined with valproate compared to not on valproate. Conclusions: Rufinamide clearance was affected by age as well as comedication in this cohort of children. The lower the age of the child the higher the RUF clearance. On comedication with valproate, RUF clearance was significantly lower in the group of younger children. Thus, in the clinic, it should be of importance to take into account the age of the child as well as the type of comedication and consider the expected differences in achieved plasma levels of rufinamide.