Pharmacodynamic Model for Warfarin under Thrombo-test Monitoring

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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.
日本医療薬学会の論文