Phenoconversion of CYP2C9 in epilepsy limits the predictive value of CYP2C9 genotype in optimizing valproate therapy

Katalin Tóth, Tamás Bdi, Ádám Kiss, Manna Temesvári, Edit Háfra, Andrea Nagy, Zsuzsa Szever, Katalin Monostory

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Aim: Since prominent role in valproate metabolism is assigned to CYP2C9 in pediatric patients, the association between children's CYP2C9-status and serum valproate concentrations or dose-requirements was evaluated. Materials & Methods: The contribution of CYP2C9 genotype and CYP2C9 expression in children (n = 50, Caucasian) with epilepsy to valproate pharmacokinetics was analyzed. Results: Valproate concentrations were significantly lower in normal expressers with CYP2C9∗1/∗1 than in low expressers or in patients carrying polymorphic CYP2C9 alleles. Consistently, the dose-requirement was substantially higher in normal expressers carrying CYP2C9∗1/∗1 (33.3 mg/kg vs 13.8-17.8 mg/kg, p < 0.0001). Low CYP2C9 expression significantly increased the ratio of poor metabolizers predictable from CYP2C9 genotype (by 46%). Conclusion: Due to the substantial downregulation of CYP2C9 expression in epilepsy, inferring patients' valproate metabolizing phenotype merely from CYP2C9 genotype results in false prediction.

Original languageEnglish
Pages (from-to)199-207
Number of pages9
JournalPersonalized Medicine
Volume12
Issue number3
DOIs
Publication statusPublished - Jun 1 2015

Keywords

  • CYP2C9 expression
  • CYP2C9 genotype
  • CYPtest
  • cytochrome P450
  • epilepsy
  • pediatric patients
  • personalized medication
  • valproate therapy

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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