A comparative study of the effect of carbamazepine and valproic acid on the pharmacokinetics and metabolic profile of topiramate at steady state in patients with epilepsy

Dorit Mimrod, Luigi M. Specchio, Malka Britzi, Emilio Perucca, Nicola Specchio, Angela La Neve, Stefan Soback, René H. Levy, Giuliana Gatti, Dennis R. Doose, Bruce E. Maryanoff, Meir Bialer

Research output: Contribution to journalArticle

Abstract

Purpose: To compare the influence of enzyme-inducing comedication and valproic acid (VPA) on topiramate (TPM) pharmacokinetics and metabolism at steady state. Methods: Three groups were assessed: (a) patients receiving TPM mostly alone (control group, n = 13); (b) patients receiving TPM with carbamazepine (CBZ; n = 13); and (c) patients receiving TPM with VPA (n = 12). TPM and its metabolites were assayed in plasma and urine by liquid chromatography-mass spectrometry (LC-MS). Results: No significant differences were found in TPM oral (CL/F) and renal (CLr) clearance between the VPA group and the control group. Mean TPM CL/F and CLr were higher in the CBZ group than in controls (2.1 vs. 1.2 L/h and 1.1 vs. 0.6L/h, respectively; p <0.05). In all groups, the urinary recovery of unchanged TPM was extensive and accounted for 42-52% of the dose (p > 0.05). Urinary recovery of 2,3-0-des-isopropylidene-TPM (2,3-diol-TPM) accounted for 3.5% of the dose in controls, 2.2% in the VPA group (p > 0.05), and 13% in the CBZ group (p <0.05). The recovery of 10-hydroxy-TPM (10-OH-TPM) was twofold higher in the CBZ group than in controls, but it accounted for only

Original languageEnglish
Pages (from-to)1046-1054
Number of pages9
JournalEpilepsia
Volume46
Issue number7
DOIs
Publication statusPublished - Jul 2005

Keywords

  • Carbamazepine
  • Drug interaction
  • Enzyme induction
  • Metabolism
  • Pharmacokinetics
  • Topiramate
  • Valproic acid

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

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