ABCC2 rs2273697 is associated with valproic acid concentrations in patients with epilepsy on valproic acid monotherapy

Pharmazie. 2018 May 1;73(5):279-282. doi: 10.1691/ph.2018.7344.

Abstract

Valproic acid (VPA), a widely used antiepileptic drug, is characterized by intensive inter-individual variability in concentration. Both efflux and influx transporters are reported to play important roles in the disposition of VPA, however, no comprehensive investigation into the association of the single nucleotide polymorphism (SNP) in ABC/SLC families with VPA concentration are reported. In the present study, we investigated the association of 12 SNPs in ABCC2, ABCC4, ABCG2, MCT1, MCT2, and OATP2B1 in 187 Chinese patients with epilepsy on VPA monotherapy with the trough concentrations of VPA. The data showed that VPA concentration in patients with ABCC2 rs2273697 AA genotype was significantly higher than that in those with GA+GG genotypes (p=0.000). The findings of the present study suggest that ABCC2 polymorphisms influence VPA concentrations in patients with epilepsy on VPA monotherapy, which may affect the treatment outcomes.

Trial registration: ClinicalTrials.gov NCT01172626.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anticonvulsants / administration & dosage
  • Anticonvulsants / pharmacokinetics*
  • Asian People / genetics
  • Epilepsy / drug therapy
  • Epilepsy / genetics*
  • Epilepsy / metabolism
  • Female
  • Genotype
  • Humans
  • Male
  • Multidrug Resistance-Associated Protein 2
  • Multidrug Resistance-Associated Proteins / genetics*
  • Multidrug Resistance-Associated Proteins / metabolism
  • Polymorphism, Single Nucleotide
  • Treatment Outcome
  • Valproic Acid / administration & dosage
  • Valproic Acid / pharmacokinetics*
  • Young Adult

Substances

  • ABCC2 protein, human
  • Anticonvulsants
  • Multidrug Resistance-Associated Protein 2
  • Multidrug Resistance-Associated Proteins
  • Valproic Acid

Associated data

  • ClinicalTrials.gov/NCT01172626