title: Low-dose naproxen interferes with the antiplatelet effects of aspirin in healthy subjects: recommendations to minimize the functional consequences.
abstract: OBJECTIVE
  To investigate whether low-dose naproxen sodium (220 mg twice a day) interferes with aspirin's antiplatelet effect in healthy subjects.
  
  
  METHODS
  We performed a crossover, open-label study in 9 healthy volunteers. They received for 6 days 3 different treatments separated by 14 days of washout: 1) naproxen 2 hours before aspirin, 2) aspirin 2 hours before naproxen, and 3) aspirin alone. The primary end point was the assessment of serum thromboxane B(2) (TXB(2)) 24 hours after the administration of naproxen 2 hours before aspirin on day 6 of treatment. In 5 volunteers, the rate of recovery of TXB(2) generation (up to 72 hours after drug discontinuation) was assessed in serum and in platelet-rich plasma stimulated with arachidonic acid (AA) or collagen.
  
  
  RESULTS
  Twenty-four hours after the last dosing on day 6 in volunteers receiving aspirin alone or aspirin before naproxen, serum TXB(2) was almost completely inhibited (median [range] 99.1% [97.4-99.4%] and 99.1% [98.0-99.7%], respectively). Naproxen given before aspirin caused a slightly lower inhibition of serum TXB(2) (median [range] 98.0% [90.6-99.4%]) than aspirin alone (P = 0.0007) or aspirin before naproxen (P = 0.0045). All treatments produced a maximal inhibition of AA-induced platelet aggregation. At 24 hours, compared with baseline, collagen-induced platelet aggregation was still inhibited by aspirin alone (P = 0.0003), but not by aspirin given 2 hours before or after naproxen. Compared with administration of aspirin alone, the sequential administration of naproxen and aspirin caused a significant parallel upward shift of the regression lines describing the recovery of platelet TXB(2).
  
  
  CONCLUSIONS
  Sequential administration of 220 mg naproxen twice a day and low-dose aspirin interferes with the irreversible inhibition of platelet cyclooxygenase 1 afforded by aspirin. The interaction was smaller when giving naproxen 2 hours after aspirin. The clinical consequences of these 2 schedules of administration of aspirin with naproxen remain to be studied in randomized clinical trials.
authors.affiliation: G. d'Annunzio University-Chieti and G. d'Annunzio University Foundation, Chieti, Italy. ppatrignani@unich.it
authors.forename: Paola
authors.initials: P
authors.lastname: Anzellotti
authors.forename: Marta L
authors.initials: ML
authors.lastname: Capone
authors.forename: Anita
authors.initials: A
authors.lastname: Jeyam
authors.forename: Stefania
authors.initials: S
authors.lastname: Tacconelli
authors.forename: Annalisa
authors.initials: A
authors.lastname: Bruno
authors.forename: Paola
authors.initials: P
authors.lastname: Tontodonati
authors.forename: Luigia
authors.initials: L
authors.lastname: Di Francesco
authors.forename: Linda
authors.initials: L
authors.lastname: Grossi
authors.forename: Giulia
authors.initials: G
authors.lastname: Renda
authors.forename: Gabriele
authors.initials: G
authors.lastname: Merciaro
authors.forename: Patrizia
authors.initials: P
authors.lastname: Di Gregorio
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Price
authors.forename: Luis A
authors.initials: LA
authors.lastname: Garcia Rodriguez
authors.forename: Paola
authors.initials: P
authors.lastname: Patrignani
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D016718:Arachidonic Acid / Q000494:pharmacology; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects*; D003094:Collagen / Q000494:pharmacology; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D009288:Naproxen / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D053657:Platelet-Rich Plasma / Q000187:drug effects; D012016:Reference Values; D013929:Thromboxane B2 / Q000097:blood; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D013929:Thromboxane B2; D009288:Naproxen; D003094:Collagen; D001241:Aspirin