en
Scientific article
English

Stereoselective interaction between piroxicam and acenocoumarol

Published inBritish journal of clinical pharmacology, vol. 41, no. 6, p. 525-530
Publication date1996
Abstract

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: Cmax+28.0% (s.d.23.8), P < 0.05; AUC(0, 24 h)+47.2% (21.5), P < 0.005; and t1/2 +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: Cmax: +9.5% (s.d.36.6), AUC(0, 24 h): + 15.4% (23.4), t1/2: +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 S-acenocoumarol 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.

Keywords
  • Acenocoumarol/administration & dosage/blood/pharmacokinetics
  • Administration, Oral
  • Adult
  • Anti-Inflammatory Agents, Non-Steroidal/administration & dosage/blood/pharmacokinetics/pharmacology
  • Anticoagulants/administration & dosage/blood/pharmacokinetics
  • Drug Interactions
  • Humans
  • Male
  • Piroxicam/administration & dosage/blood/pharmacokinetics/pharmacology
  • Stereoisomerism
Citation (ISO format)
BONNABRY, Pascal et al. Stereoselective interaction between piroxicam and acenocoumarol. In: British journal of clinical pharmacology, 1996, vol. 41, n° 6, p. 525–530.
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Article (Published version)
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Identifiers
ISSN of the journal0306-5251
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