PHARMACODYNAMIC OPTIMIZATION OF WARFARIN THERAPY

Pharmacokinetic-pharmacodynamic information regarding warfarin is used to produce a predictive model based on the idea that pharmacodynamic variability is more important than pharmacokinetic variability in the overall dose-response variability to warfarin. A modification of the m aximum effect model is tested on a group of patients initiating oral a nticoagulation with warfarin. Results indicate that the model can acco unt for at least half of the total variation in maintenance doses obse rved (sample coefficient of determination, 0.53) and offer the physici an a framework for dose requirements at the onset of therapy. The basi c prediction equation is as follows: Maintenance dose = (11/internatio nal normalized ratio) - 1, with a coefficient of correlation of 0.73 ( 95% confidence limits, 0.46-0.88). Application of this model may impro ve on the traditional empiric approach to warfarin dose adjustment.