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.

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Keywords adolescent, anticoagulation, child, infant, pharmacogenomics, phenprocoumon, thrombosis
Persistent URL dx.doi.org/10.2217/pgs-2018-0095, hdl.handle.net/1765/110929
Journal Pharmacogenomics
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Citation
Maagdenberg, H. (Hedy), Bierings, M, van Ommen, C.H, van der Meer, F.J.M, Appel, I.M, Tamminga, R, … Maitland-van der Zee, A-H. (2018). Effects of age and genetic variations in VKORC1, CYP2C9 and CYP3A4 on the phenprocoumon dose in pediatric patients. Pharmacogenomics, 19(15), 1195–1202. doi:10.2217/pgs-2018-0095