Rising dose study of safety and tolerance of flunarizine.
In a recent NIH-sponsored parallel-group placebo-controlled blinded study of flunarizine for the treatment of partial-onset seizures, the flunarizine serum concentration was controlled to a constant level among patients in order to reduce response variability. Flunarizine was found to exhibit modest anti-epileptic efficacy. A potential criticism of this study is that the chosen controlled concentration was too low to determine optimal efficacy. As a participating center in this study we investigated the effect of higher doses of open-label flunarizine on seizure frequency in 16 patients with refractory partial seizures. Following the completion of the blinded placebo/flunarizine phase, all patients were initiated at the flunarizine dose calculated to result in a serum concentration of 60 ng.ml-1. The dose was subsequently increased each 8-12 weeks to a maximum of 2.7 times the initial dose. On the initial maintenance flunarizine dose, seizure control was improved, with an average seizure reduction of 47% compared to pre-blinded-phase baseline. When higher doses were administered, adverse reactions were more common yet improved seizure control did not occur in most patients. These findings complement those of the concentration-controlled NIH study and suggest that appropriate flunarizine doses were utilized in that study.
Handforth
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Department of Veterans Affairs, Medical Center West Los Angeles, CA 90073, USA.
Mai
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Treiman
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D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D004828:Epilepsies, Partial / Q000097:blood / Q000188:drug therapy*; D005260:Female; D005444:Flunarizine / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged
D000927:Anticonvulsants; D005444:Flunarizine