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No clinically relevant effect of lornoxicam intake on acenocoumarol pharmacokinetics and pharmacodynamics
U P Masche1, K M Rentsch, A von Felten
1University Hospital, Zurich, Switzerland.
Objective:
To investigate the effect of lornoxicam co-administration on acenocoumarol pharmacokinetics and pharmacodynamics.
Methods:
In an open crossover study, six healthy male volunteers received racemic acenocoumarol (10 mg) orally without/with lornoxicam co-administration (8 mg twice daily).
Results:
The median (range) areas under the concentration-time curve (AUC) for (R)-acenocoumarol were 3458 (3035-7312) microg x h 1(-1) in the absence of and 3667 (2907-7741) microg x h 1(-1) in the presence of lornoxicam. The corresponding values for (S)-acenocoumarol were 479 (381-853) microg x h 1(-1) and 612 (425-1241) microg x h 1(-1). The differences were not statistically significant. Lornoxicam co-administration did not influence the free fractions or acenocoumarol's effect on factor II and VII activities. Simulations based on the results of a model-based analysis predicted that in the case of lornoxicam co-administration, the factor VII activity of a person in steady-state at 26% will remain between 14% and 32%.
Conclusion:
Co-administration of lornoxicam at the upper limit of recommended doses does not alter the pharmocokinetics of the clinically relevant (R)-acenocoumarol or the anticoagulant activity of acenocoumarol. These data clearly differ from the results of previous studies, which showed clinically relevant influences of lornoxicam on warfarin kinetics and of piroxicam on acenocoumarol kinetics.