Pharmacodynamic Model for Warfarin under Thrombo-test Monitoring

To determine a pharmacodynamic model for warfarin under thrombo-test (TT) monitoring, we examined the correlation between steady state TT values, warfarin dosage and serum concentration in patients receiving warfarin treatment. Based on the results, we developed a pharmacodynamic model relating TT values to free warfarin concentrations.We studied 19 cardiac patients receiving warfarin anticoagulant therapy in whom warfarin serum concentrations and TT values were considered to be in a steady state. While no correlation was observed between steady-state TT values and either warfarin dosage per kilogram body weight or total warfarin concentration, a significant negative correlation was observed between steady-state TT values and free warfarin concentrations (r=-0.561, p<0.05). We then developed a pharmacodynamic model expressing the relationship between steady-state TT values and free warfarin concentrations using nonlinear least-squares fitting. The AIC (Akaike's Information Criterion) of the sigmoid Emax model was 171.2, a value less than the AICs of the linear, log-linear and Emax models.In conclusion, a sigmoid Emax model expressing the relationship between TT values and free warfarin concentration is an appropriate pharmacodynamic model for warfarin when TT values are used as an indicator of coagulability.