Pharmacokinetic-pharmacodynamic investigation of a possible interaction between steady-state temocapril and warfarin in healthy subjects

Objective: To investigate the influence of temocapril treatment on the phar macokinetics and pharmacodynamics of warfarin. Design: Twenty-four healthy volunteers were administered individually adjus ted doses of warfarin to attain Quick values (prothrombin time) in the rang e 1.4 to 1.8 International Normalised Ratio (INR). Subsequently, a double-b lind, two-way crossover treatment with 20mg temocapril and placebo, each on ce daily for 2 weeks, was added to the stable warfarin regimen. Results: Pharmacokinetic [maximum plasma concentration (C-max) and area und er the concentration-time curve (AUC)] and pharmacodynamic [maximum effect (E-max) and total area under the effect-time curve (AUE) of Quick and parti al thromboplastin time (PTT)] measurements were performed over one dosage i nterval at the end of each treatment. Temocapril did not exert any influenc e on the pharmacokinetic and pharmacodynamic parameters of warfarin. The 90 % confidence intervals around each point estimate were within the range 80 to 125%. Conclusions: No clinically relevant effect of temocapril on the pharmacokin etics and pharmacodynamics of warfarin was detected in healthy subjects.