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Stereoselective interaction between piroxicam and acenocoumarol
Author(s) -
BONNABRY P.,
DESMEULES J.,
RUDAZ S.,
LEEMANN T.,
VEUTHEY J.L.,
DAYER P.
Publication year - 1996
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.1996.03558.x
Subject(s) - acenocoumarol , piroxicam , medicine , pharmacology , warfarin , atrial fibrillation , alternative medicine , pathology
1 An open‐label study was performed to assess the effect of piroxicam on the pharmacokinetics of acenocoumarol enantiomers. 2 Eight healthy male volunteers received an oral dose of 4 mg rac ‐acenocoumarol on days 1 and 8, plus 40 mg piroxicam orally 2 h before the anticoagulant on day 8. R‐ and S‐acenocoumarol, piroxicam and their metabolites were measured in plasma over a 24 h interval. 3 The pharmacokinetics of R‐acenocoumarol were markedly modified by piroxicam: C max +28.0% (s.d.23.8), P <0.05; AUC(0, 24 h)+47.2% (21.5), P <0.005; and t 1/2 +38.0% (34.5), P <0.01. A concomitant decrease of CL/ F was observed: −30.8% (10.0), P <0.0001. A similar, but statistically non‐significant trend, was observed on the S‐enantiomer: C max : +9.5% (s.d.36.6), AUC(0, 24 h): +15.4% (23.4), t 1/2 : +19.9% (42.0), and CL/ F: −9.8% (20.5). V/F remained unchanged for both enantiomers. 4 Piroxicam plasma AUC(0, 24 h) correlated closely with R‐ and Sacenocoumarol AUCs on day 1 ( r =0.901, P <0.005 and r =0.797, P <0.05, respectively), as well as with the difference of AUC between days 1 and 8 for R‐acenocoumarol ( r =0.903, P <0.001) and S‐acenocoumarol ( r =0.711, P <0.05). 5 Piroxicam markedly reduced acenocoumarol enantiomer clearance, with a greater effect on the more active R‐isomer. This interaction, which occurs in addition to the well documented pharmacodynamic one (effect on platelets), is expected to result in increased anticoagulant effect.