Clinical experience with topiramate dosing and serum levels in patients with epilepsy

Seizure. 2006 Mar;15(2):86-92. doi: 10.1016/j.seizure.2005.11.003. Epub 2006 Jan 6.

Abstract

Objective: To investigate the relevance of serum topiramate (TPM) levels (SL) monitoring in the clinical management of epileptic patients.

Methods: Twenty-seven patients with different epileptic syndromes on TPM therapy were studied. TPM was used as add-on in 26 patients, only in one as monotherapy de novo; one case changed from TPM as add-on to TPM monotherapy. The mean follow-up time was 11 months. TPM SL were measured by fluorescence polarization immunoassay.

Results: We analyzed the TPM SL in 43 samples from 27 patients. Mean TPM dose was 3.9mg/kg, mean TPM SL 13.43mumol/l. The mean level to dose ratio (LDR) was 3.63mumol/l/mg/kg. Four patients became seizure-free, all with TPM dosages lower than the mean. Eleven patients had at least 50% seizure reduction. The comedication with enzyme-inducing AED significantly reduced TPM SL and LDR. On the other hand, the influence of valproic acid (VPA) on TPM LDR was not univocal. Indeed, patients younger than 15 years showed SL values lower than the adults did, although not significant.

Conclusion: We could not detect a direct relationship between high TPM SL and efficacy neither between high TPM SL and tolerability. However, the data we collected seem to favour the hypothesis that high TPM dosage and SL might be associated to a greater probability to reduce seizure severity.

MeSH terms

  • Adolescent
  • Adult
  • Anticonvulsants / administration & dosage*
  • Anticonvulsants / blood
  • Anticonvulsants / pharmacokinetics
  • Child
  • Child, Preschool
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Epilepsy / blood
  • Epilepsy / drug therapy*
  • Female
  • Fructose / administration & dosage
  • Fructose / analogs & derivatives*
  • Fructose / blood
  • Fructose / pharmacokinetics
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Prospective Studies
  • Regression Analysis
  • Topiramate

Substances

  • Anticonvulsants
  • Topiramate
  • Fructose