Free and total plasma concentrations of carbamazepine and carbamazepine-10,11-epoxide in epileptic patients: Diurnal fluctuations and relationship with side effects

R. Riva, M. Contin, F. Albani, E. Perucca, G. Ambrosetto, G. Gobbi, P. Coltelli, G. Procaccianti, A. Baruzzi

Research output: Contribution to journalArticle

Abstract

The diurnal fluctuations in free and total plasma levels of carbamazepine (CBZ) and carbamazepine-10, ll-epoxide (CBZ-E) and their relationship with intermittent side effects were examined in 10 epileptic patients stabilized on chronic CBZ therapy alone or in combination with phenobarbital (PB). With a t.i.d. or q.i.d. dosing schedule, total plasma levels of CBZ and CBZ-E fluctuated to a similar extent (average 34% and 29%, respectively). The diurnal changes in free levels of both compounds mirrored closely those of the total levels. Free fraction values ranged from 13 to 26% for CBZ and from 24 to 66% for CBZ-E. Owing to the lower protein binding of the metabolite, CBZ-E/CBZ ratios were higher in plasma water (0.49) than in whole plasma (0.22). A good correlation was found between both total and free CBZ levels and dose-related side effects (diplopia, nystagmus). On the other hand, no apparent relationship was found between side effects and either total or free plasma CBZ-E. The correlation with the presence of neurological signs of toxicity for the sum of CBZ + CBZ-E levels was no better than that observed for CBZ levels alone. These data do not support the hypothesis that CBZ-E contributes significantly to the development of dose-related side effects in CBZ-treated patients.

Original languageEnglish
Pages (from-to)408-413
Number of pages6
JournalTherapeutic Drug Monitoring
Volume6
Issue number4
Publication statusPublished - 1984

Fingerprint

Carbamazepine
Plasmas
carbamazepine epoxide
Diplopia
Eye movements
Epoxy Compounds
Phenobarbital
Metabolites
Protein Binding

Keywords

  • Carbamazepine
  • Carbamazepine-epoxide
  • Diurnal fluctuations
  • Free plasma concentrations
  • Side effects

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Toxicology
  • Health, Toxicology and Mutagenesis
  • Biochemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Public Health, Environmental and Occupational Health

Cite this

@article{854cfec2467d48c0985914b5458872ff,
title = "Free and total plasma concentrations of carbamazepine and carbamazepine-10,11-epoxide in epileptic patients: Diurnal fluctuations and relationship with side effects",
abstract = "The diurnal fluctuations in free and total plasma levels of carbamazepine (CBZ) and carbamazepine-10, ll-epoxide (CBZ-E) and their relationship with intermittent side effects were examined in 10 epileptic patients stabilized on chronic CBZ therapy alone or in combination with phenobarbital (PB). With a t.i.d. or q.i.d. dosing schedule, total plasma levels of CBZ and CBZ-E fluctuated to a similar extent (average 34{\%} and 29{\%}, respectively). The diurnal changes in free levels of both compounds mirrored closely those of the total levels. Free fraction values ranged from 13 to 26{\%} for CBZ and from 24 to 66{\%} for CBZ-E. Owing to the lower protein binding of the metabolite, CBZ-E/CBZ ratios were higher in plasma water (0.49) than in whole plasma (0.22). A good correlation was found between both total and free CBZ levels and dose-related side effects (diplopia, nystagmus). On the other hand, no apparent relationship was found between side effects and either total or free plasma CBZ-E. The correlation with the presence of neurological signs of toxicity for the sum of CBZ + CBZ-E levels was no better than that observed for CBZ levels alone. These data do not support the hypothesis that CBZ-E contributes significantly to the development of dose-related side effects in CBZ-treated patients.",
keywords = "Carbamazepine, Carbamazepine-epoxide, Diurnal fluctuations, Free plasma concentrations, Side effects",
author = "R. Riva and M. Contin and F. Albani and E. Perucca and G. Ambrosetto and G. Gobbi and P. Coltelli and G. Procaccianti and A. Baruzzi",
year = "1984",
language = "English",
volume = "6",
pages = "408--413",
journal = "Therapeutic Drug Monitoring",
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TY - JOUR

T1 - Free and total plasma concentrations of carbamazepine and carbamazepine-10,11-epoxide in epileptic patients

T2 - Diurnal fluctuations and relationship with side effects

AU - Riva, R.

AU - Contin, M.

AU - Albani, F.

AU - Perucca, E.

AU - Ambrosetto, G.

AU - Gobbi, G.

AU - Coltelli, P.

AU - Procaccianti, G.

AU - Baruzzi, A.

PY - 1984

Y1 - 1984

N2 - The diurnal fluctuations in free and total plasma levels of carbamazepine (CBZ) and carbamazepine-10, ll-epoxide (CBZ-E) and their relationship with intermittent side effects were examined in 10 epileptic patients stabilized on chronic CBZ therapy alone or in combination with phenobarbital (PB). With a t.i.d. or q.i.d. dosing schedule, total plasma levels of CBZ and CBZ-E fluctuated to a similar extent (average 34% and 29%, respectively). The diurnal changes in free levels of both compounds mirrored closely those of the total levels. Free fraction values ranged from 13 to 26% for CBZ and from 24 to 66% for CBZ-E. Owing to the lower protein binding of the metabolite, CBZ-E/CBZ ratios were higher in plasma water (0.49) than in whole plasma (0.22). A good correlation was found between both total and free CBZ levels and dose-related side effects (diplopia, nystagmus). On the other hand, no apparent relationship was found between side effects and either total or free plasma CBZ-E. The correlation with the presence of neurological signs of toxicity for the sum of CBZ + CBZ-E levels was no better than that observed for CBZ levels alone. These data do not support the hypothesis that CBZ-E contributes significantly to the development of dose-related side effects in CBZ-treated patients.

AB - The diurnal fluctuations in free and total plasma levels of carbamazepine (CBZ) and carbamazepine-10, ll-epoxide (CBZ-E) and their relationship with intermittent side effects were examined in 10 epileptic patients stabilized on chronic CBZ therapy alone or in combination with phenobarbital (PB). With a t.i.d. or q.i.d. dosing schedule, total plasma levels of CBZ and CBZ-E fluctuated to a similar extent (average 34% and 29%, respectively). The diurnal changes in free levels of both compounds mirrored closely those of the total levels. Free fraction values ranged from 13 to 26% for CBZ and from 24 to 66% for CBZ-E. Owing to the lower protein binding of the metabolite, CBZ-E/CBZ ratios were higher in plasma water (0.49) than in whole plasma (0.22). A good correlation was found between both total and free CBZ levels and dose-related side effects (diplopia, nystagmus). On the other hand, no apparent relationship was found between side effects and either total or free plasma CBZ-E. The correlation with the presence of neurological signs of toxicity for the sum of CBZ + CBZ-E levels was no better than that observed for CBZ levels alone. These data do not support the hypothesis that CBZ-E contributes significantly to the development of dose-related side effects in CBZ-treated patients.

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