Effects of age and genetic variations in VKORC1, CYP2C9 and CYP3A4 on the phenprocoumon dose in pediatric patients

Pharmacogenomics. 2018 Oct;19(15):1195-1202. doi: 10.2217/pgs-2018-0095. Epub 2018 Sep 12.

Abstract

Aim: To study the effects of clinical and genetic factors on the phenprocoumon dose requirement in pediatric patients and to develop a dosing algorithm.

Methods: Pediatric patients who used phenprocoumon were invited to participate in a retrospective follow-up study. Clinical information and genotypes of genetic variations in CYP2C9, VKORC1, CYP4F2, CYP2C18 and CYP3A4 were collected and tested with linear regression for association with phenprocoumon dose requirement.

Results: Of the 41 patients included in the analysis, age, VKORC1, CYP2C9*2/*3 and CYP3A4*1B were statistically significantly associated with dose requirement, and together explained 80.4% of the variability in phenprocoumon dose requirement.

Conclusion: Our study reveals that age and genetic variations explain a significant part of the variability in phenprocoumon dose requirement in pediatric patients.

Keywords: adolescent; anticoagulation; child; infant; pharmacogenomics; phenprocoumon; thrombosis.

MeSH terms

  • Adolescent
  • Age Factors
  • Anticoagulants / administration & dosage*
  • Child
  • Child, Preschool
  • Cytochrome P-450 CYP2C9 / genetics*
  • Cytochrome P-450 CYP3A / genetics*
  • Female
  • Follow-Up Studies
  • Genotype
  • Humans
  • Infant
  • Male
  • Pharmacogenetics / methods
  • Phenprocoumon / administration & dosage*
  • Polymorphism, Single Nucleotide / genetics*
  • Retrospective Studies
  • Vitamin K Epoxide Reductases / genetics*

Substances

  • Anticoagulants
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human
  • VKORC1 protein, human
  • Vitamin K Epoxide Reductases
  • Phenprocoumon