Influence of sex, age, weight, and carbamazepine dose on serum concentrations, concentration ratios, and level/dose ratios of carbamazepine and its metabolites

Ther Drug Monit. 1994 Oct;16(5):469-76. doi: 10.1097/00007691-199410000-00005.

Abstract

We have conducted a comprehensive study in a group of epileptic children (25 boys and 30 girls) receiving carbamazepine (CBZ) monotherapy. The influence of sex, age, weight, and CBZ daily dose on serum CBZ, carbamazepine-10,11-epoxide (CBZ-E), and trans-10,11-dihydroxy-10,11-dihydro-carbamazepine (CBZ-H) concentrations, concentration ratios, and level/dose ratios were investigated. Compared with girls, boys required significantly larger CBZ dose and showed higher CBZ apparent clearances and lower level/dose ratios of CBZ and its metabolites. There were no significant differences between boys and girls in serum concentrations, concentration ratios, and free fractions of CBZ and its metabolites, although there were trends that boys had slightly higher concentration ratios. The relationship analysis suggested that there was a dose-dependent autoinduction of CBZ metabolism, and CBZ metabolism was decreased as patients mature, as measured by weight and age. Age showed a significant positive relationship with the free fractions of CBZ and its metabolites, indicating decreased protein binding of CBZ and its metabolites with the increase of age. Serum CBZ concentration is not a reliable index of CBZ dose, as there is only a weak correlation between them. Serum CBZ-H concentration showed strong positive correlations with CBZ dose and might be a valuable index in assessing patient compliance. The influence of sex, body weight, age, and CBZ dose on CBZ and its metabolites should be taken into consideration in further clinical studies.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / blood*
  • Body Weight / physiology*
  • Carbamazepine / analogs & derivatives*
  • Carbamazepine / blood*
  • Carbamazepine / therapeutic use*
  • Child
  • Child, Preschool
  • Dose-Response Relationship, Drug
  • Epilepsy / blood*
  • Epilepsy / drug therapy*
  • Female
  • Humans
  • Male
  • Sex Factors

Substances

  • Carbamazepine
  • 10,11-dihydro-10,11-dihydroxy-5H-dibenzazepine-5-carboxamide
  • carbamazepine epoxide