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Low-dose naproxen interferes with the antiplatelet effects of aspirin in healthy subjects: Recommendations to minimize the functional consequences

2010; Wiley; Volume: 63; Issue: 3 Linguagem: Inglês

10.1002/art.30175

1529-0131

Paola Anzellotti, Marta L. Capone, Anita Jeyam, Stefania Tacconelli, Annalisa Bruno, P. Tontodonati, Luigia Di Francesco, L. Grossi, Giulia Renda, Gabriele Merciaro, Patrizia Di Gregorio, Thomas S. Price, Luis A. Garcı́a Rodrı́guez, Paola Patrignani,

Analytical Methods in Pharmaceuticals

To investigate whether low-dose naproxen sodium (220 mg twice a day) interferes with aspirin's antiplatelet effect in healthy subjects.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.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).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.