Clinical reappraisal of the influence of drug-transporter polymorphisms in epilepsy

Expert Opin Drug Metab Toxicol. 2018 May;14(5):505-512. doi: 10.1080/17425255.2018.1473377. Epub 2018 May 28.

Abstract

Although novel antiepileptic drugs (AEDs) have been recently released, the issue of drug resistance in epileptic patients remains unsolved and largely unpredictable. Areas covered: We aim to assess the clinical impact of genetic variations that may influence the efficacy of medical treatment in epilepsy patients. Indeed, many genes, including genes encoding drug transporters (ABCB1), drug targets (SCN1A), drug-metabolizing enzymes (CYP2C9, CYP2C19), and human leucocyte antigen (HLA) proteins, may regulate the mechanisms of drug resistance in epilepsy. This review specifically focuses on the ABC genes, which encode multidrug resistance-associated proteins (MRPs) and may reduce the blood-brain barrier penetration of anticonvulsant AEDs. Expert opinion: Drug resistance remains a crucial problem in epilepsy patients. Pharmacogenomic studies may improve our understanding of drug responses and drug resistance by exploring the impact of gene variants and predicting drug responses and tolerability.

Keywords: Genetic polymorphisms; antiepileptic drugs; refractory epilepsy; transporters.

Publication types

  • Review

MeSH terms

  • ATP-Binding Cassette Transporters / genetics*
  • Animals
  • Anticonvulsants / pharmacokinetics
  • Anticonvulsants / therapeutic use*
  • Biological Transport / genetics
  • Blood-Brain Barrier / metabolism
  • Drug Resistance / genetics
  • Epilepsy / drug therapy*
  • Epilepsy / genetics
  • Humans
  • Pharmacogenetics
  • Polymorphism, Genetic
  • Tissue Distribution

Substances

  • ATP-Binding Cassette Transporters
  • Anticonvulsants