Increasing Plasma Concentration Tolerability Study of Flunarizine in Comedicated Epileptic Patients

David M. Treiman, Gordon W. Pledger, Christopher DeGiorgio, Jia‐Yeong ‐Y Tsay, James J. Cereghino

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Twelve patients with intractable partial seizures [4 receiving carbamazepine (CBZ), 4 phenytoin (PHT), and 4 both] entered a study of the tolerability of flunarizine (FNR) at specified plasma concentrations. After an 8‐week baseline period, a single‐dose pharmacoki‐netic study was performed for each patient to calculate a loading dose and maintenance dosage necessary to achieve a target plasma FNR concentration of 30 ng/ml. The first 8 patients received the loading dose (as divided doses) during a 1‐week hospitalization and the maintenance dosage for the ensuing 8 weeks. These patients proceeded to treatment periods with target concentrations of 60 and then 120 ng/ml, using doses based on an assumed linear relation between dose and plasma concentration. The last 4 patients were studied only at the 120‐ng/ml target level. Results indicated that this procedure successfully approximated target levels of 30 and 60 ng/ ml, but observed concentrations in the last period exceeded the 120‐ng/ml target level and continued to increase with time, often necessitating a dosage reduction owing to intolerability. Calculated doses for a given target concentration varied by a factor of 12. The most frequently reported adverse experiences were sedation and increased fatigue; reports of dizziness, headache, and lethargy were also common. Based on this study, a target concentration of at least 60 but <120 ng/ml is recommended for a controlled clinical trial of the antiepileptic efficacy of FNR.

Original languageEnglish (US)
Pages (from-to)944-953
Number of pages10
Issue number5
StatePublished - Sep 1993
Externally publishedYes


  • Anticonvulsants
  • Carbamazepine
  • Clinical trials
  • Drug toxicity
  • Epilepsy
  • Flunarizine
  • Partial seizures
  • Pharmacokinetics
  • Phenytoin

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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