WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Warfarin is a widely used anticoagulant with a low therapeutic index. • There is wide interindividual variation in the pharmacokinetics and pharmacodynamics of warfarin which is also reflected in the warfarin dose requirement. • CYP2C9 and VKORC1 polymorphisms have been shown to affect warfarin dose requirement. However a large amount of the variation in warfarin dose remains unaccounted for. WHAT THIS STUDY ADDS• Our findings suggest that in patients who are on long-term warfarin therapy, INR : plasma 7-hydroxywarfarin concentration correlates well with warfarin requirement and also accounts for a large amount of variation in warfarin dose. AIMSTo assess the correlation between plasma total warfarin concentration, plasma 7-hydroxywarfarin concentration and INR and the weekly doses of warfarin in patients on long-term anticoagulation. METHODSTwenty-five patients on long-term anticoagulation with warfarin were studied. Plasma total warfarin and 7-hydroxywarfarin concentrations and INR were determined. Equations were derived with the weekly warfarin dose as the dependent variable and plasma total warfarin concentration : plasma 7-hydroxywarfarin concentration, INR : plasma total warfarin concentration and INR : plasma 7-hydroxywarfarin concentration as independent variables. RESULTSThere was a good correlation between INR : plasma total warfarin concentration and the weekly dose of warfarin (y = 46.73e CONCLUSIONSPharmacokinetic parameters along with INR seem to correlate with the weekly doses of warfarin in patients on long-term anticoagulation. These parameters may therefore be useful for predicting warfarin doses.
Objectives:Cytochrome P450 2C9 (CYP2C9) is a member of cytochrome P450 (CYP) family that accounts for nearly 18% of the total CYP protein content in the human liver microsomes and catalyzes almost 15–20% of the drugs. Considering the paucity of data on the polymorphisms of CYP2C9 in Western Indian population, the present study was conducted to evaluate the prevalence of CYP2C9 polymorphisms (*1, *2 and *3) and correlate it with the activity using flurbiprofen (FLB) as a probe drug.Materials and Methods:A 100 mg FLB capsule was administered to 298 healthy adult participants. Venous blood samples were analyzed at 2 h postdose for the estimation of FLB and 4-hydroxy FLB. Metabolic ratio (MR) was calculated to determine the extent of poor metabolizer (PM) and rapid metabolizer status using probit plot. Genotyping of CYP2C9 polymorphism was performed using polymerase chain reaction-restriction fragment length polymorphism technique.Results:Of the total 298 participants, phenotype was assessable in 288 and genotype was performed in 289 participants. The median (range) MR of the study population was 6.6 (1.65–66.05). Five participants were found to be PMs by phenotype. Of the total 289 participants, 209 (72.3%) (66.7, 77.2) had CYP2C9*1/*1, 25 (8.7%) (5.8, 12.7) with CYP2C9*1/*2, 55 (19%) (14.8, 24.1) had CYP2C9*1/*3, 3 (1%) (0.3, 3.3) had CYP2C9*2/*3 genotype. A significant association between phenotype and genotype was observed.Conclusion:To conclude, the present study found significant association of CYP2C9 activity by both phenotype and genotype and these findings have to be corroborated in different kinds of patients.
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