FLUNARIZINE OF LIMITED VALUE IN CHILDREN WITH INTRACTABLE EPILEPSY

Fourteen ambulatory children and adolescents with intractable epilepsy were studied in an open phase II study to investigate the pharmacokin etics and pharmacodynamics of flunarizine as an add-on treatment. Flun arizine was given in increasing doses starting with 0.1-0.3 mg/kg/day until effect was observed or a steady-state plasma concentration of 50 -60 ng/ml was reached. Treatment was continued for 3 months at steady state. Pharmacokinetics were determined during the immediate posttreat ment period. Positive antiepileptic effect (greater than or equal to 5 0% reduction in seizure frequency) was observed in 4 of 14 patients (2 9%; 95% CI: 52-5), Independently of antiepileptic effect, 10 of 14 par ents (71.4%; 95% CI: 95-48) observed positive cognitive effects. In al l patients treatment was withdrawn due to either lack of effect or wei ght gain. Flunarizine was rapidly absorbed; mean time of peak concentr ation (T-max) was 2.7 hours (range: 1-8). The mean terminal half-life was 23.2 days (range: 7-48), the total plasma clearance of flunarizine per fraction of the dose absorbed (CL(p)/F) was 0.28 ml/min/kg (range : 0.07-042), and the volume of distribution of flunarizine per fractio n of the dose absorbed (Vd/F) was 187 L/kg (range: 99-348). We conclud e that flunarizine (0.1-0.3 mg/kg/day) seems to be of limited antiepil eptic value in children with intractable epilepsy. The pharmacokinetic profile of flunarizine complicates its clinical use.