It is possible that between patient differences in warfarin dose requirements is contributed to by patient age, body size, genotype, vitamin K and lipoprotein status and that knowledge of the extent of these could provide the basis for induction regimens modified according to these characteristics. We therefore set out, in patients receiving chronic therapy with warfarin with stable control of anticoagulation, to measure plasma concentrations of (R)- and (S)-warfarin, vitamin K, triglycerides and determine the CYP2C9 genotype and to correlate these with dosage and INR in order to identify any significant relationships which might be useful as predictors of the anticoagulant response.

On arrival at the clinic in the morning, following an overnight fast, a blood sample was taken from each patient for CYP2C9 genotyping and for determination of venous INR, and plasma vitamin K, (R)-& (S)-warfarin and triglyceride concentrations. Patients' demographic details were also recorded.

One hundred and twenty one patients were recruited to the study. Genotyping for CYP2C9 showed that 74 patients were homozygous wild-type (*1/*1), 30 were heterozygous *1/*2 and 15 were heterozygous *1/*3 genotype. One patient was *2/*3 and one *3/*3. Mean warfarin daily dose requirement in milligram fell from 4.06 ± 1.72 in homozygous wild-type patients, to 3.63 ± 1.78 for *1 *2 and 2.70 ± 1.36 for *1*3 positive. The multiple linear regression model for warfarin dose indicated significant contributions from age (r=0.41; p<0.001), genotype (r=0.24; p<0.005), and age and genotype together (r=0.45; p<0.1). Although there were significant linear correlations between wafarin dose and body surface area (r=0.21; p=0.02), body weight (r=0.25; p=0.005) and plasma vitamin K concentration (r=0.18; p<0.05) none of these variables made a significant contribution to the regression model for warfarin dose. CYP2C9 genotype had a significant effect on (S)- warfarin clearance (r=0.34; p<0.0001) but none on (R)- warfarin clearance.

It is anticipated that using dosing regimens modified to take account of the contribution of age and CYP2C9 genotype has the potential to improve the safety of warfarin therapy.