Abstract |
Fourteen ambulatory children and adolescents with intractable epilepsy were studied in an open phase II study to investigate the pharmacokinetics and pharmacodynamics of flunarizine as an add-on treatment. Flunarizine 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 posttreatment period. Positive antiepileptic effect (> or = 50% reduction in seizure frequency) was observed in 4 of 14 patients (29%; 95% CI: 52-5). Independently of antiepileptic effect, 10 of 14 parents (71.4%; 95% CI: 95-48) observed positive cognitive effects. In all patients treatment was withdrawn due to either lack of effect or weight gain. Flunarizine was rapidly absorbed; mean time of peak concentration (Tmax) 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 (CLp/F) was 0.28 ml/min/kg (range: 0.07-042), and the volume of distribution of flunarizine per fraction of the dose absorbed (Vd/F) was 187 L/kg (range: 99-348). We conclude that flunarizine (0.1-0.3 mg/kg/day) seems to be of limited antiepileptic value in children with intractable epilepsy. The pharmacokinetic profile of flunarizine complicates its clinical use.
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Authors | K Hoppu, A R Nergårdh, A S Eriksson, O Beck, E Forssblad, L O Boréus |
Journal | Pediatric neurology
(Pediatr Neurol)
Vol. 13
Issue 2
Pg. 143-7
(Sep 1995)
ISSN: 0887-8994 [Print] United States |
PMID | 8534279
(Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anticonvulsants
- Flunarizine
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Topics |
- Adolescent
- Anticonvulsants
(administration & dosage, adverse effects, pharmacokinetics)
- Biological Availability
- Child
- Child, Preschool
- Dose-Response Relationship, Drug
- Drug Administration Schedule
- Drug Therapy, Combination
- Electroencephalography
(drug effects)
- Epilepsy
(blood, drug therapy)
- Female
- Flunarizine
(administration & dosage, adverse effects, pharmacokinetics)
- Half-Life
- Humans
- Male
- Metabolic Clearance Rate
(physiology)
- Weight Gain
(drug effects)
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