Effects of age and genetic variations in VKORC1, CYP2C9 and CYP3A4 on the phenprocoumon dose in pediatric patients
Maagdenberg, Hedy; Bierings, Marc B.; Van Ommen, C. Heleen; Van Der Meer, Felix J.M.; Appel, Inge M.; Tamminga, Rienk Y.J.; Cessie, Saskia Le; Swen, Jesse J.; Van Der Straaten, Tahar; De Boer, Anthonius; Maitland-Van Der Zee, Anke H.
(2018) Pharmacogenomics, volume 19, issue 15, pp. 1195 - 1202
(Article)
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,
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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, article, clinical article, controlled study, drug therapy, female, follow up, genetic variation, genotype, human, linear regression analysis, male, pediatric patient, retrospective study, cytochrome P450 2C18, cytochrome P450 2C9, cytochrome P450 3A4, endogenous compound, Taverne
ISSN: 1462-2416
Publisher: Future Medicine Ltd.
(Peer reviewed)
