Interactions of valproic acid with carbamazepine and its metabolites' concentrations, concentration ratios, and level/dose ratios in epileptic children

H. Liu, M. R. Delgado, R. H. Browne

Research output: Contribution to journalReview article

13 Scopus citations

Abstract

In two groups of epileptic children receiving carbamazepine (CBZ) therapy with or without valproic acid (VPA) comedication, we investigate the drug interactions of VPA on serum CBZ and its metabolites' concentrations, concentration ratios, and level/dose ratios. Serum total and free CBZ-10,11- epoxide (CBZ-E) concentrations are significantly increased in patients taking CBZ plus VPA, together with higher CBZ-E/CBZ concentration ratios and CBZ-E level/dose ratios. These results reflect the accumulation of CBZ-E. The decreased concentration ratios of trans-10,11-dihydroxy-10,11-dihydro-CBZ (CBZ-H)/CBZ-E observed in patients taking CBZ plus VPA suggest an inhibition in the biotransformation from CBZ-E to CBZ-H. Significant negative correlations are found between serum VPA level and CBZ-H/CBZ-E concentration ratios, indicating that the inhibition of CBZ-E hydrolysis by VPA may depend on the concentration of VPA (total or free CBZ-H/CBZ-E concentration ratio = VPA-2.004e(7.942+0.014*VPA) or = VPA-2.004e(8.299+0.014*VPA) respectively). VPA concentration also shows significant positive correlations with CBZ-E and CBZ level/dose ratios. Patients taking CBZ plus VPA have significant higher free fractions of CBZ and CBZ-E than do patients on CBZ alone, suggesting a protein-binding displacement by VPA.

Original languageEnglish (US)
Pages (from-to)1-12
Number of pages12
JournalClinical Neuropharmacology
Volume18
Issue number1
DOIs
StatePublished - Jan 1 1995

Keywords

  • Carbamazepine
  • Carbamazepine-diol
  • Carbamazepine-epoxide
  • Drug interaction
  • Epileptic children
  • Valproic acid

ASJC Scopus subject areas

  • Pharmacology
  • Clinical Neurology
  • Pharmacology (medical)

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