UNIGE document Scientific Article
previous document  unige:6868  next document
add to browser collection
Title

Stereoselective interaction between piroxicam and acenocoumarol

Authors
Leemann, T.
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/pharmacokineticsAdministration, OralAdultAnti-Inflammatory Agents, Non-Steroidal/administration & dosage/blood/pharmacokinetics/pharmacologyAnticoagulants/administration & dosage/blood/pharmacokineticsDrug InteractionsHumansMalePiroxicam/administration & dosage/blood/pharmacokinetics/pharmacologyStereoisomerism
Identifiers
PMID: 8799517
Full text
Article (Published version) (324 Kb) - document accessible for UNIGE members only Limited access to UNIGE
Structures
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

257 hits

7 downloads

Update

Deposited on : 2010-06-15

Export document
Format :
Citation style :