title: Pharmacodynamic interaction of naproxen with low-dose aspirin in healthy subjects.
abstract: OBJECTIVE
  We investigated the occurrence of pharmacodynamic interaction between low-dose aspirin and naproxen.
  
  
  BACKGROUND
  The uncertainty of cardioprotection by naproxen has encouraged its combination with aspirin in patients with arthritis and cardiovascular disease.
  
  
  METHODS
  The incubation of washed platelets with naproxen for 5 min before the addition of aspirin reduced the irreversible inhibition of thromboxane (TX)B(2) production by aspirin. The pharmacodynamic interaction between the two drugs was then investigated in four healthy volunteers who received aspirin (100 mg daily) for 6 days and then the combination of aspirin and naproxen for further 6 days: aspirin 2 h before naproxen (500 mg, twice-daily dosing). After 14 days of washout, naproxen was given 2 h before aspirin for further 6 days.
  
  
  RESULTS
  The inhibition of serum TXB(2) production (index of platelet cyclooxygenase [COX]-1 activity) and platelet aggregation ex vivo and urinary 11-dehydro-TXB(2) levels (index of TXB(2) biosynthesis in vivo) by aspirin alone (99 +/- 0.2%, 95 +/- 0.6%, and 81 +/- 4%, respectively) was not significantly altered by the co-administration of naproxen, given either 2 h after aspirin or in reverse order. In a second study, the concurrent administration of a single dose of aspirin and naproxen did not affect platelet TXB(2) production and aggregation at 1 h after dosing, when aspirin alone causes maximal inhibitory effect. Moreover, the rapid recovery of platelet COX-1 activity and function supports the occurrence of a pharmacodynamic interaction between naproxen and aspirin.
  
  
  CONCLUSIONS
  Naproxen interfered with the inhibitory effect of aspirin on platelet COX-1 activity and function. This pharmacodynamic interaction might undermine the sustained inhibition of platelet COX-1 that is necessary for aspirin's cardioprotective effects.
authors.affiliation: Department of Medicine and Center of Excellence on Aging, School of Medicine, G. d'Annunzio University, Chieti, Italy.
authors.forename: Marta L
authors.initials: ML
authors.lastname: Capone
authors.forename: Maria G
authors.initials: MG
authors.lastname: Sciulli
authors.forename: Stefania
authors.initials: S
authors.lastname: Tacconelli
authors.forename: Marilena
authors.initials: M
authors.lastname: Grana
authors.forename: Emanuela
authors.initials: E
authors.lastname: Ricciotti
authors.forename: Giulia
authors.initials: G
authors.lastname: Renda
authors.forename: Patrizia
authors.initials: P
authors.lastname: Di Gregorio
authors.forename: Gabriele
authors.initials: G
authors.lastname: Merciaro
authors.forename: Paola
authors.initials: P
authors.lastname: Patrignani
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001168:Arthritis / Q000188:drug therapy; D001241:Aspirin / Q000008:administration & dosage* / Q000494:pharmacology; D002318:Cardiovascular Diseases / Q000188:drug therapy; D051545:Cyclooxygenase 1; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006801:Humans; D066298:In Vitro Techniques; D008565:Membrane Proteins; D009288:Naproxen / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases; D013929:Thromboxane B2 / Q000037:antagonists & inhibitors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D008565:Membrane Proteins; D013929:Thromboxane B2; D009288:Naproxen; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin