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Increasing Plasma Concentration Tolerability Study of Flunarizine in Comedicated Epileptic Patients
Author(s) -
Treiman David M.,
Pledger Gordon W.,
DeGiorgio Christopher,
Tsay JiaYeong,
Cereghino James J.
Publication year - 1993
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1157.1993.tb02116.x
Subject(s) - tolerability , flunarizine , epilepsy , medicine , pharmacology , psychiatry , adverse effect , calcium
Summary: 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.