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Integration of genetic, clinical, and INR data to refine warfarin dosing
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.ORCID iD: 0000-0002-6368-2622
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2010 (English)In: Clinical Pharmacology and Therapeutics, ISSN 0009-9236, E-ISSN 1532-6535, Vol. 87, no 5, 572-578 p.Article in journal (Refereed) Published
Abstract [en]

Well-characterized genes that affect warfarin metabolism (cytochrome P450 (CYP) 2C9) and sensitivity (vitamin K epoxide reductase complex 1 (VKORC1)) explain one-third of the variability in therapeutic dose before the international normalized ratio (INR) is measured. To determine genotypic relevance after INR becomes available, we derived clinical and pharmacogenetic refinement algorithms on the basis of INR values (on day 4 or 5 of therapy), clinical factors, and genotype. After adjusting for INR, CYP2C9 and VKORC1 genotypes remained significant predictors (P < 0.001) of warfarin dose. The clinical algorithm had an R(2) of 48% (median absolute error (MAE): 7.0 mg/week) and the pharmacogenetic algorithm had an R(2) of 63% (MAE: 5.5 mg/week) in the derivation set (N = 969). In independent validation sets, the R(2) was 26-43% with the clinical algorithm and 42-58% when genotype was added (P = 0.002). After several days of therapy, a pharmacogenetic algorithm estimates the therapeutic warfarin dose more accurately than one using clinical factors and INR response alone.

Place, publisher, year, edition, pages
2010. Vol. 87, no 5, 572-578 p.
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Medical and Health Sciences
URN: urn:nbn:se:uu:diva-124510DOI: 10.1038/clpt.2010.13ISI: 000276956300013PubMedID: 20375999OAI: oai:DiVA.org:uu-124510DiVA: diva2:317617
Available from: 2010-05-04 Created: 2010-05-04 Last updated: 2016-02-19

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Wadelius, Mia
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Clinical pharmacogenomics and osteoporosisDepartment of Medical SciencesUCR-Uppsala Clinical Research Center
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