Effects of age and genetic variations in VKORC1, CYP2C9 and CYP3A4 on the phenprocoumon dose in pediatric patients-Reference-Cited by-同舟云学术

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

Published:2018-10 Issue:15 Volume:19 Page:1195-1202
ISSN:1462-2416
Container-title:Pharmacogenomics
language:en
Short-container-title:Pharmacogenomics

Author:

Maagdenberg Hedy¹,Bierings Marc B²,van Ommen C Heleen³,van der Meer Felix JM⁴,Appel Inge M³,Tamminga Rienk YJ⁵,Cessie Saskia le⁶⁷,Swen Jesse J⁸,der Straaten Tahar van⁸,Boer Anthonius de¹,Maitland-van der Zee Anke H¹⁹

Affiliation:

1. Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands

2. Department of Pediatric Stem Cell Transplantation, Princess Maxima Center for pediatric oncology/Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands

3. Department of Pediatric Oncology/Hematology, Erasmus MC/Sophia Children's Hospital, Erasmus University Medical Center, Rotterdam, The Netherlands

4. Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands

5. Department of Pediatric Hematology, University Medical Center Groningen, Groningen, The Netherlands

6. Department of Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands

7. Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands

8. Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands

9. Department of Respiratory Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands

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.

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

Link

https://www.futuremedicine.com/doi/pdf/10.2217/pgs-2018-0095

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