RISING DOSE STUDY OF SAFETY AND TOLERANCE OF FLUNARIZINE

In a recent NIH-sponsored parallel-group placebo-controlled blinded st udy of flunarizine for the treatment of partial-onset seizures, the fl unarizine serum concentration was controlled to a constant level among patients in order to reduce response variability. Flunarizine was fou nd 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 w e investigated the effect of higher doses of open-label flunarizine on seizure frequency in 16 patients with refractory partial seizures. Fo llowing the completion of the blinded placebo/flunarizine phase, all p atients were initiated at the flunarizine dose calculated to result in a serum concentration of 60 ng . ml(-1). The dose was subsequently in creased each 8-12 weeks to a maximum of 2.7 times the initial dose. On the initial maintenance flunarizine dose, seizure control was improve d, with an average seizure reduction of 47% compared to pre-blinded-ph ase baseline. When higher doses were administered, adverse reactions w ere more common yet improved seizure control did not occur in most pat ients. These findings complement those of the concentration-controlled NIH study and suggest that appropriate flunarizine doses were utilize d in that study.