Current induction and maintenance dosing regimens do not take into account the genetic and environmental factors which affect patient response to warfarin and thus dose requirement. Although we had earlier demonstrated that patient age, CYP2C9 genotype and body-size significantly contribute to warfarin dose, the results did not allow prediction of dose across the normally wide patient age range or for individual CYP2C9 allelic variants because of the relatively small number of patients studied. This study is an extension of the earlier study investigating the impact of genetic and individual characteristics on warfarin dose requirements in patients receiving long-term warfarin therapy.

Two hundred and ninety-seven patients (aged 22–90 years) with stable warfarin dose requirements over the previous 3 months and with an International Normalized Ratio (INR) within the target range of 2.0–3.0 were recruited into the study. A 20 ml blood sample was taken at the anticoagulation clinic for determination of CYP2C9 genotype, venous INR and plasma R- and S-warfarin concentration. The mean warfarin daily dose requirement was 4.08 ± 2.13 mg in patients homozygous wild-type for CYP2C9, 3.56 ± 1.82 mg in CYP2C9*1*2 patients, 2.7 ± 1.38 mg in CYP2C9*1*3 patients, 1.92 ± 1.12 mg in CYP2C9*2*2 patients and 1.58 ± 0.79 mg in CYP2C9*2*3 or *3*3 patients. Mean warfarin daily dose requirements fell by 0.6–0.7 mg per decade of life between the ages of 20–90 years. The multiple regression model for warfarin dose demonstrated a significant contribution from age (r² = 14.9%; p < 0.0001), genotype (r² = 12.9%; p < 0.0001) and height (r²= 5.9%; p < 0.001). However the model containing the factors of age, genotype and height was the best predictor for dose requirement (r²= 34.3%; p < 0.0001).

The results of this study demonstrated that patient genotype in the expression of CYP2C9 enzyme responsible for the metabolism of S-warfarin, age and height collectively make significant contribution to warfarin dose requirements. Based on these findings we intend to examine a more individualized warfarin dosing regimen in patients requiring anticoagulation with the aim of improving the safety of warfarin therapy.