Increasing plasma concentration tolerability study of flunarizine in comedicated epileptic patients

D. M. Treiman, G. W. Pledger, C. DeGiorgio, J. Y. Tsay, James Cereghino

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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 pharmacokinetic 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

Original languageEnglish (US)
Pages (from-to)944-953
Number of pages10
JournalEpilepsia
Volume34
Issue number5
StatePublished - 1993
Externally publishedYes

Fingerprint

Flunarizine
Maintenance
Lethargy
Carbamazepine
Phenytoin
Dizziness
Fatigue
Headache
Seizures
Hospitalization
Pharmacokinetics

Keywords

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

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Treiman, D. M., Pledger, G. W., DeGiorgio, C., Tsay, J. Y., & Cereghino, J. (1993). Increasing plasma concentration tolerability study of flunarizine in comedicated epileptic patients. Epilepsia, 34(5), 944-953.

Increasing plasma concentration tolerability study of flunarizine in comedicated epileptic patients. / Treiman, D. M.; Pledger, G. W.; DeGiorgio, C.; Tsay, J. Y.; Cereghino, James.

In: Epilepsia, Vol. 34, No. 5, 1993, p. 944-953.

Research output: Contribution to journalArticle

Treiman, DM, Pledger, GW, DeGiorgio, C, Tsay, JY & Cereghino, J 1993, 'Increasing plasma concentration tolerability study of flunarizine in comedicated epileptic patients', Epilepsia, vol. 34, no. 5, pp. 944-953.
Treiman, D. M. ; Pledger, G. W. ; DeGiorgio, C. ; Tsay, J. Y. ; Cereghino, James. / Increasing plasma concentration tolerability study of flunarizine in comedicated epileptic patients. In: Epilepsia. 1993 ; Vol. 34, No. 5. pp. 944-953.
@article{85451a840a1f42a89e152fd92c73e250,
title = "Increasing plasma concentration tolerability study of flunarizine in comedicated epileptic patients",
abstract = "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 pharmacokinetic 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",
keywords = "Anticonvulsants, Carbamazepine, Clinical trials, Drug toxicity, Epilepsy, Flunarizine, Partial seizures, Pharmacokinetics, Phenytoin",
author = "Treiman, {D. M.} and Pledger, {G. W.} and C. DeGiorgio and Tsay, {J. Y.} and James Cereghino",
year = "1993",
language = "English (US)",
volume = "34",
pages = "944--953",
journal = "Epilepsia",
issn = "0013-9580",
publisher = "Wiley-Blackwell",
number = "5",

}

TY - JOUR

T1 - Increasing plasma concentration tolerability study of flunarizine in comedicated epileptic patients

AU - Treiman, D. M.

AU - Pledger, G. W.

AU - DeGiorgio, C.

AU - Tsay, J. Y.

AU - Cereghino, James

PY - 1993

Y1 - 1993

N2 - 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 pharmacokinetic 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

AB - 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 pharmacokinetic 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

KW - Anticonvulsants

KW - Carbamazepine

KW - Clinical trials

KW - Drug toxicity

KW - Epilepsy

KW - Flunarizine

KW - Partial seizures

KW - Pharmacokinetics

KW - Phenytoin

UR - http://www.scopus.com/inward/record.url?scp=0027369045&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027369045&partnerID=8YFLogxK

M3 - Article

C2 - 8404751

AN - SCOPUS:0027369045

VL - 34

SP - 944

EP - 953

JO - Epilepsia

JF - Epilepsia

SN - 0013-9580

IS - 5

ER -