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Variant CYP2C9 Alleles and Warfarin Concentrations in Patients Receiving Low-Dose Versus Average-Dose Warfarin Therapy

Pharmacy Department, Rockdale Medical Center, Conyers, Andrearredman{at}yahoo.com

Jack Zheng, MS

Department of Chemistry, Georgia State University, Atlanta

Shahab A. Shamsi, PhD

Department of Chemistry, Georgia State University, Atlanta

Jingguo Huo, PhD

Department of Clinical Science and Administration, College of Pharmacy, Texas Medical Center, Houston

Edward J. Kelly, PhD

Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle

Rodney J.Y. Ho, PhD

Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle

Denise M. Ritchie, MBA, PharmD, CACP

Anticoagulation Monitoring Service, Atlanta Veterans Affairs Medical Center, Decatur, Georgia

Yuen Yi Hon, PharmD

Clinical Pharmacokinetics Research Laboratory, Clinical Center Pharmacy Department, National Institutes of Health, Bethesda, Maryland

This study compared the frequency of variant cytochrome P450 2C9 (CYP2C9) alleles and warfarin S/R concentration ratio in patients who required low-dose (<2.5 mg/day) and average-dose (5 ± 0.5 mg/day) warfarin. Patients who achieved a therapeutic international normalized ratio were recruited from the Atlanta Veterans Affairs Medical Center anticoagulation clinic. CYP2C9*2 and *3 alleles were determined by validated Taqman allelic discrimination assays. Warfarin S and R concentrations were determined by chiral capillary electrochromatography with electrospray ionization mass spectrometry. At least 1 variant allele was found in 66.7% and 22.2% of patients in the low-dose and average-dose groups, respectively (P = .001, ²). The warfarin S/R concentration ratio was 0.665 (range, 0.162-3.58) and 0.452 (range, 0.159-2.36) for patients receiving low-dose and average-dose therapy, respectively ( P = .097). A warfarin requirement of <2.5 mg/day and an elevated warfarin S/R concentration ratio were each associated with a higher frequency of variant CYP2C9 alleles.

Key Words: warfarin • cytochrome P-450 enzyme system • genetic polymorphisms • R-warfarin concentrations • S-warfarin concentrations

This version was published on January 1, 2008

Clinical and Applied Thrombosis/Hemostasis, Vol. 14, No. 1, 29-37 (2008)
DOI: 10.1177/1076029607304403


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