P-glycoprotein: a clue to vitamin K antagonist stabilization

Pharmacogenomics. 2015 Jan;16(2):129-36. doi: 10.2217/pgs.14.164.

Abstract

Background: Acenocoumarol is a vitamin K antagonist used in some European countries. As warfarin, this drug is characterized by a narrow therapeutic index and a large interindividual variability.

Aim: The objective of this study was to assess the involvement of ABCB1 polymorphisms on acenocoumarol treatment.

Materials & methods: An observational cohort study was conducted to assess whether there is an association between the presence of the allelic variants of the ABCB1 gene coding for P-glycoprotein and acenocoumarol stabilization and daily doses during the first 35 days of treatment.

Results: One hundred and fifteen patients met the inclusion criteria. The results of the clinical study showed that carriers of ABCB1 c.3435TT were more rapidly stabilized than wild-type patients (HR: 2.97, 95% CI: 1.23-7.18; p = 0.02). The same tendency was observed for the ABCB1 c.2677GT and 2677TT genotypes compared with ABCB1 c.2677GG. The ABCB1 c.2677TT genotype was also associated with a significant increase in doses of acenocoumarol (p = 0.03), the same tendency was observed with the ABCB1 c.3435TT genotype compared with the wild-type patients.

Conclusion: These data suggest that ABCB1 polymorphisms could be involved in the response to acenocoumarol treatment.

Trial registration: ClinicalTrials.gov NCT01492777.

Keywords: ABCB1; P-glycoprotein; acenocoumarol; drug transporter; gene polymorphism; pharmacogenetics; vitamin K antagonists.

Publication types

  • Observational Study

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / drug effects
  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • Acenocoumarol / administration & dosage
  • Acenocoumarol / therapeutic use*
  • Anticoagulants / administration & dosage
  • Anticoagulants / therapeutic use*
  • Female
  • Genotype
  • Humans
  • International Normalized Ratio
  • Male
  • Middle Aged
  • Polymorphism, Genetic / genetics
  • Prospective Studies
  • Thromboembolism / prevention & control
  • Treatment Outcome
  • Vitamin K / antagonists & inhibitors*

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • Anticoagulants
  • Vitamin K
  • Acenocoumarol

Associated data

  • ClinicalTrials.gov/NCT01492777