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Scientific Article
unige:6868 
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Stereoselective interaction between piroxicam and acenocoumarol |
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| Authors | ||
| Published in | British journal of clinical pharmacology. 1996, vol. 41, no. 6, p. 525-30 | |
| 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 | |
| Identifiers | PMID: 8799517 | |
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| 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. 525-30. https://archive-ouverte.unige.ch/unige:6868 |
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