Flunarizine for treatment of partial seizures: Results of a concentration–controlled trial

Gordon W. Pledger, J. C. Sackellares, D. M. Treiman, J. M. Pellock, F. S. Wright, M. Mikati, J. T. Sahlroot, J. Y. Tsay, M. E. Drake, L. Olson, C. A. Handforth, W. R. Garnett, S. Schachter, H. J. Kupferberg, M. R. Ashworth, C. McCormick, D. Leiderman, I. M. Kapetanovic, S. Driscoll, K. O' HaraC. D. Torchin, J. Gentile, A. Kay, J. J. Cereghino

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29 Scopus citations

Abstract

The National Institutes of Health sponsored a randomized, double-blind, multicenter, placebo-controlled trial of flunarizine (FNR) in epileptic patients receiving concomitant phenytoin (PHT) or carbamazepine (CBZ). Because of FNR’s long half-life (up to 7 weeks), a parallel rather than crossover design was used. Each patient received an individualized loading dose and maintenance dosage targeted at a 60-ng/ml plasma FNR concentration. Of 93 patients randomized, 92 provided seizure data for the full 25-week treatment period; one placebo-treated patient dropped out for personal reasons. Fifty-four patients received CBZ only, nine received PHT only, and 30 received both CBZ and PHT. Eighty-seven patients had a history of complex partial seizures, and 60 had secondarily generalized seizures. Eight patients discontinued FNR prematurely, all because of adverse neurologic or psychiatric signs or symptoms; depression was the specific cause in three cases. Calculated maintenance dosages, based on single-dose pharmacokinetic profiles, ranged from 7 to 138 mg/day (mean, 40 mg/day). Plasma FNR concentrations generally exceeded the target, with the highest concentrations observed immediately after loading; excluding the first three treatment weeks and all concentrations after a FNR dosage change, the median plasma FNR concentration was 71.7 ng/ml. The percent reduction from baseline seizure rate was statistically greater (p = 0.002) in the FNR-treated group (mean, 24.4%) than in the placebo-treated group (mean, 5.7%).

Original languageEnglish (US)
Pages (from-to)1830-1836
Number of pages7
JournalNeurology
Volume44
Issue number10
DOIs
StatePublished - Oct 1994

ASJC Scopus subject areas

  • Clinical Neurology

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    Pledger, G. W., Sackellares, J. C., Treiman, D. M., Pellock, J. M., Wright, F. S., Mikati, M., Sahlroot, J. T., Tsay, J. Y., Drake, M. E., Olson, L., Handforth, C. A., Garnett, W. R., Schachter, S., Kupferberg, H. J., Ashworth, M. R., McCormick, C., Leiderman, D., Kapetanovic, I. M., Driscoll, S., ... Cereghino, J. J. (1994). Flunarizine for treatment of partial seizures: Results of a concentration–controlled trial. Neurology, 44(10), 1830-1836. https://doi.org/10.1212/wnl.44.10.1830