Variant CYP2C9 alleles and warfarin concentrations in patients receiving low-dose versus average-dose warfarin therapy.
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, chi(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.
Redman
Andrea R
AR
Pharmacy Department, Rockdale Medical Center, Conyers, GA 30012, USA. Andrearredman@yahoo.com
Zheng
Jack
J
Shamsi
Shahab A
SA
Huo
Jingguo
J
Kelly
Edward J
EJ
Ho
Rodney J Y
RJ
Ritchie
Denise M
DM
Hon
Yuen Yi
YY
D000368:Aged; D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065729:Cytochrome P-450 CYP2C9; D004305:Dose-Response Relationship, Drug; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics / Q000379:methods*; D013237:Stereoisomerism; D014859:Warfarin / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry*
D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases