Publication:
Integration of genetic, clinical, and INR data to refine warfarin dosing

Issued Date

2010-05-01

Resource Type

Article

ISSN

15326535
00099236

DOI

10.1038/clpt.2010.13

Other identifier(s)

2-s2.0-77951498679

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

Clinical Pharmacology and Therapeutics. Vol.87, No.5 (2010), 572-578

Suggested Citation

P. Lenzini, M. Wadelius, S. Kimmel, J. L. Anderson, A. L. Jorgensen, M. Pirmohamed, M. D. Caldwell, N. Limdi, J. K. Burmester, M. B. Dowd, P. Ngchaisuksiri, A. R. Bss, J. Chen, N. Eriksson, A. Rane, J. D. Lindh, J. F. Carlquist, B. D. Horne, G. Grice, P. E. Milligan, C. Eby, J. Shin, H. Kim, D. Kurnik, C. M. Stein, G. McMillin, R. C. Pendleton, R. L. Berg, P. Deloukas, B. F. Gage Integration of genetic, clinical, and INR data to refine warfarin dosing. Clinical Pharmacology and Therapeutics. Vol.87, No.5 (2010), 572-578. doi:10.1038/clpt.2010.13 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/29698

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Title

Integration of genetic, clinical, and INR data to refine warfarin dosing

Author(s)

P. Lenzini
 M. Wadelius
 S. Kimmel
 J. L. Anderson
 A. L. Jorgensen
 M. Pirmohamed
 M. D. Caldwell
 N. Limdi
 J. K. Burmester
 M. B. Dowd
 P. Ngchaisuksiri
 A. R. Bss
 J. Chen
 N. Eriksson
 A. Rane
 J. D. Lindh
 J. F. Carlquist
 B. D. Horne
 G. Grice
 P. E. Milligan
 C. Eby
 J. Shin
 H. Kim
 D. Kurnik
 C. M. Stein
 G. McMillin
 R. C. Pendleton
 R. L. Berg
 P. Deloukas
 B. F. Gage

Other Contributor(s)

Washington University in St. Louis
 Uppsala Universitet
 University of Pennsylvania
 Intermountain Medical Center
 University of Liverpool
 Marshfield Clinic
 University of Alabama
 Clinical Pharmacy Cardiac Risk Service
 Mahidol University
 Hospital for Special Surgery - New York
 Akademiska Sjukhuset
 Karolinska Institutet
 St. Louis College of Pharmacy
 Inje University
 Vanderbilt University
 University of Utah
 Wellcome Trust Sanger Institute

Abstract

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 R2of 48% (median absolute error (MAE): 7.0mg/week) and the pharmacogenetic algorithm had an R2of 63% (MAE: 5.5mg/week) in the derivation set (N = 969). In independent validation sets, the R2was 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.

Keyword(s)

Medicine
 Pharmacology, Toxicology and Pharmaceutics

Availability

URI

https://repository.li.mahidol.ac.th/handle/123456789/29698

Collections

Scopus 2006-2010