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

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.