Relationship of S/R warfarin ratio with CYP2C9 genotypes in Pakistani population

Abstract

Warfarin is administered as a racemic preparation of R- and S-enantiomers. S-warfarin is more potent than Rwarfarin, so changes in blood levels of S-warfarin affect the anticoagulant response. This study was carried out to determine the effect of CYP2C9*2 and CYP2C9*3 polymorphisms on S/R warfarin ratio. A single blood sample was collected 12-16 hours after drug administration from 170 stable patients fulfilling the criteria. Genotyping of the CYP2C9 polymorphisms was done by polymerase chain reaction-restriction fragment length polymorphism assay. Sand R-warfarin enantiomers extraction from plasma was accomplished by a validated HPLC method. The concentration of S-warfarin was significantly different among CYP2C9 genotypes (p =0.018) whereas there was no effect on Rwarfarin (p =0.134). There was statistically significant effect of different CYP2C9 genotypes on S/R warfarin ratio (p=0.000). It is concluded that CYP2C9 polymorphisms influence CYP2C9 enzymatic activity in turn affecting Swarfarin levels but not R-warfarin, thus leading to different S/R warfarin enantiomers ratio among different CYP2C9 genotypes.