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 maximum effect model is tested on a group of patients initiating oral anticoagulation with warfarin. Results indicate that the model can account for at least half of the total variation in maintenance doses observed (sample coefficient of determination, 0.53) and offer the physician a framework for dose requirements at the onset of therapy. The basic prediction equation is as follows: Maintenance dose = (11/international normalized ratio) ‐ 1, with a coefficient of correlation of 0.73 (95% confidence limits, 0.46‐0.88). Application of this model may improve on the traditional empiric approach to warfarin dose adjustment. Clinical Pharmacology and Therapeutics (1994) 55, 597–601; doi: 10.1038/clpt.1994.74