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 journalArticlepeer-review

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

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

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