title: Absence of interaction of fondaparinux sodium with aspirin and piroxicam in healthy male volunteers.
abstract: OBJECTIVE
  Patients undergoing major orthopaedic surgery who are being treated with fondaparinux sodium for prevention of venous thromboembolism may be receiving treatment for coronary artery disease or chronic inflammatory disease of the joints or arthritis. Two separate studies assessed any possible interaction between fondaparinux sodium at steady state and aspirin (acetylsalicylic acid) or piroxicam in healthy volunteers.
  
  
  METHODS
  In the first study a single dose of aspirin 975mg was assessed initially, followed by single doses of aspirin or placebo on the fourth day of an 8-day regimen of subcutaneous fondaparinux sodium (10mg once daily). The second study was a three-way crossover, double-blind, randomised study which investigated fondaparinux sodium 10mg + placebo, fondaparinux sodium 10mg + piroxicam 20mg, or placebo + piroxicam 20mg.
  
  
  METHODS
  Both studies obtained plasma concentration-time profiles of fondaparinux sodium administered alone and with aspirin or piroxicam. Noncompartmental parameters - peak concentration, trough concentration, time to reach peak concentration, and area under the concentration-time curve - were obtained. Both studies measured the pharmacodynamic parameters bleeding time and activated partial thromboplastin time (aPTT). Safety was monitored.
  
  
  CONCLUSIONS
  Neither aspirin nor piroxicam influenced the pharmacokinetics of fondaparinux sodium at steady state. Two hours after administration, prolongation of bleeding time with aspirin alone or with aspirin plus fondaparinux sodium was significantly greater than with fondaparinux sodium alone (p = 0.003 and p = 0.004, respectively). No significant differences were observed between aspirin alone or aspirin + fondaparinux sodium in effect on bleeding time. A small decrease in collagen-induced platelet aggregation was observed after administration of piroxicam alone or piroxicam + fondaparinux sodium. A small effect on aPTT was observed; it was similar for fondaparinux sodium whether administered alone or in combination with either aspirin or piroxicam. No serious adverse events were reported.
authors.affiliation: Sanofi-Synthelabo Groupe, Montpellier, France. celine.ollier@sanofi-synthelabo.com
authors.forename: Céline
authors.initials: C
authors.lastname: Ollier
authors.forename: Richard A
authors.initials: RA
authors.lastname: Faaij
authors.forename: Alix
authors.initials: A
authors.lastname: Santoni
authors.forename: Thierry
authors.initials: T
authors.lastname: Duvauchelle
authors.forename: Paul M M
authors.initials: PM
authors.lastname: van Haard
authors.forename: Rik C
authors.initials: RC
authors.lastname: Schoemaker
authors.forename: Adam F
authors.initials: AF
authors.lastname: Cohen
authors.forename: Rik
authors.initials: R
authors.lastname: de Greef
authors.forename: Jacobus
authors.initials: J
authors.lastname: Burggraaf
mesh_terms: D000328:Adult; D001241:Aspirin / Q000494:pharmacology*; D001760:Bleeding Time; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions; D005343:Fibrinolytic Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D000077425:Fondaparinux; D006801:Humans; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D010894:Piroxicam / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D011134:Polysaccharides / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D011134:Polysaccharides; D010894:Piroxicam; D000077425:Fondaparinux; D001241:Aspirin