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Stereoselective interaction between piroxicam and acenocoumarol
P Bonnabry1, J Desmeules, S Rudaz
1Division of Clinical Pharmacology, University Hospitals, Geneva, Switzerland.
British Journal of Clinical Pharmacology
|June 1, 1996
Summary
Piroxicam significantly impacts acenocoumarol pharmacokinetics, reducing clearance of both enantiomers, particularly the R-isomer. This drug interaction may increase the anticoagulant effect of acenocoumarol.
Area of Science:
- Pharmacology
- Drug Interactions
- Clinical Pharmacokinetics
Background:
- Acenocoumarol is an anticoagulant with enantiomers R and S.
- Piroxicam is a non-steroidal anti-inflammatory drug.
- Understanding drug interactions is crucial for patient safety.
Purpose of the Study:
- To investigate the pharmacokinetic interaction between piroxicam and acenocoumarol enantiomers.
- To determine how piroxicam affects the absorption, distribution, metabolism, and excretion of acenocoumarol.
Main Methods:
- An open-label study involving eight healthy male volunteers.
- Administration of oral rac-acenocoumarol with and without piroxicam.
- Measurement of plasma concentrations of acenocoumarol enantiomers and piroxicam over 24 hours.
Main Results:
- Piroxicam significantly increased the Cmax, AUC(0-24h), and t1/2 of R-acenocoumarol, while decreasing its CL/F.
- A similar, though not statistically significant, trend was observed for S-acenocoumarol.
- Piroxicam plasma AUC correlated with acenocoumarol AUCs and the change in AUC.
Conclusions:
- Piroxicam markedly reduces acenocoumarol enantiomer clearance, with a greater effect on the R-isomer.
- This pharmacokinetic interaction, alongside the known pharmacodynamic effect, is expected to enhance the anticoagulant activity of acenocoumarol.
- Caution is advised when co-administering piroxicam and acenocoumarol due to potential for increased anticoagulant effect.