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, James Cereghino

Research output: Contribution to journalArticle

29 Citations (Scopus)

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
StatePublished - 1994
Externally publishedYes

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Flunarizine
Seizures
Carbamazepine
Phenytoin
Placebos
Therapeutics
Maintenance
National Institutes of Health (U.S.)
Cross-Over Studies
Nervous System
Signs and Symptoms
Psychiatry
Half-Life
Pharmacokinetics

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Clinical Neurology
  • Neuroscience(all)

Cite this

Pledger, G. W., Sackellares, J. C., Treiman, D. M., Pellock, J. M., Wright, F. S., Mikati, M., ... Cereghino, J. (1994). Flunarizine for treatment of partial seizures: Results of a concentration–controlled trial. Neurology, 44(10), 1830-1836.

Flunarizine for treatment of partial seizures : Results of a concentration–controlled trial. / Pledger, Gordon 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.; O' Hara, K.; Torchin, C. D.; Gentile, J.; Kay, A.; Cereghino, James.

In: Neurology, Vol. 44, No. 10, 1994, p. 1830-1836.

Research output: Contribution to journalArticle

Pledger, GW, Sackellares, JC, Treiman, DM, Pellock, JM, Wright, FS, Mikati, M, Sahlroot, JT, Tsay, JY, Drake, ME, Olson, L, Handforth, CA, Garnett, WR, Schachter, S, Kupferberg, HJ, Ashworth, MR, McCormick, C, Leiderman, D, Kapetanovic, IM, Driscoll, S, O' Hara, K, Torchin, CD, Gentile, J, Kay, A & Cereghino, J 1994, 'Flunarizine for treatment of partial seizures: Results of a concentration–controlled trial', Neurology, vol. 44, no. 10, pp. 1830-1836.
Pledger GW, Sackellares JC, Treiman DM, Pellock JM, Wright FS, Mikati M et al. Flunarizine for treatment of partial seizures: Results of a concentration–controlled trial. Neurology. 1994;44(10):1830-1836.
Pledger, Gordon 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. ; O' Hara, K. ; Torchin, C. D. ; Gentile, J. ; Kay, A. ; Cereghino, James. / Flunarizine for treatment of partial seizures : Results of a concentration–controlled trial. In: Neurology. 1994 ; Vol. 44, No. 10. pp. 1830-1836.
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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{\%}).",
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T2 - Results of a concentration–controlled trial

AU - Pledger, Gordon W.

AU - Sackellares, J. C.

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AU - Pellock, J. M.

AU - Wright, F. S.

AU - Mikati, M.

AU - Sahlroot, J. T.

AU - Tsay, J. Y.

AU - Drake, M. E.

AU - Olson, L.

AU - Handforth, C. A.

AU - Garnett, W. R.

AU - Schachter, S.

AU - Kupferberg, H. J.

AU - Ashworth, M. R.

AU - McCormick, C.

AU - Leiderman, D.

AU - Kapetanovic, I. M.

AU - Driscoll, S.

AU - O' Hara, K.

AU - Torchin, C. D.

AU - Gentile, J.

AU - Kay, A.

AU - Cereghino, James

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N2 - 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%).

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