Genotype-based dosage of acenocoumarol in highly-sensitive geriatric patients

Int J Clin Pharmacol Ther. 2015 Mar;53(3):206-10. doi: 10.5414/CP202206.

Abstract

Objective: Our aim was to determinate the acenocoumarol dose requirement in highly sensitive geriatric patients, based on a minimum of genotype (VKORC1 and CYP2C9) data.

Methods: We used a Gaussian kernel density estimation test to identify patients highly sensitive to the drug and PHARMACHIP®-Cuma test (Progenika Biopharma, SA, Grifols, Spain) to determine the CYP2C9 and VKORC1 genotype.

Results: All highly sensitive geriatric patients were taking ≤5.6 mg/week of acenocoumarol (AC), and 86% of these patients presented the following genotypes: CYP2C9*1/*3 or CYP2C9*1/*2 plus VKORC1 A/G, CYP2C9*3/*3, or VKORC1 A/A.

Conclusion: VKORC1 A and CYP2C9*2 and/or *3 allelic variants extremely influence on AC dose requirement of highly sensitive geriatric patients. These patients display acenocoumarol dose requirement of ≤5.6 mg/week.

MeSH terms

  • Acenocoumarol / administration & dosage*
  • Acenocoumarol / blood
  • Acenocoumarol / pharmacokinetics
  • Age Factors
  • Aged, 80 and over
  • Aging / genetics*
  • Aging / metabolism
  • Anticoagulants / administration & dosage*
  • Anticoagulants / blood
  • Anticoagulants / pharmacokinetics
  • Cytochrome P-450 CYP2C9 / genetics*
  • Cytochrome P-450 CYP2C9 / metabolism
  • Drug Dosage Calculations
  • Drug Monitoring
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Male
  • Oligonucleotide Array Sequence Analysis
  • Pharmacogenetics
  • Phenotype
  • Pilot Projects
  • Vitamin K Epoxide Reductases / genetics*
  • Vitamin K Epoxide Reductases / metabolism

Substances

  • Anticoagulants
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • VKORC1 protein, human
  • Vitamin K Epoxide Reductases
  • Acenocoumarol