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(Circulation. 2004;109:1468-1471.)
© 2004 American Heart Association, Inc.

Brief Rapid Communications

Clinical Pharmacology of Platelet, Monocyte, and Vascular Cyclooxygenase Inhibition by Naproxen and Low-Dose Aspirin in Healthy Subjects

Marta L. Capone, PharmD; Stefania Tacconelli, PharmD; Maria G. Sciulli, PhD; Marilena Grana, MD; Emanuela Ricciotti, PharmD; Pietro Minuz, MD; Patrizia Di Gregorio, MD; Gabriele Merciaro; Carlo Patrono, MD; Paola Patrignani, PhD

From the Department of Medicine and Center of Excellence on Aging, G. d’Annunzio University, School of Medicine, and G. d’Annunzio University Foundation, Chieti (M.L.C., S.T., M.G.S., M.G., E.R., C.P., P.P.); the Department of Pharmacology, University of Rome La Sapienza (C.P.); SS. Annunziata Hospital, Chieti (P.D., G.M.); and the Department of Biomedical and Surgical Sciences, University of Verona (P.M.), Italy.

Correspondence to Paola Patrignani, PhD, Dipartimento di Medicina e Scienze dell’Invecchiamento, Università G. d’Annunzio, Via dei Vestini 31, 66013 Chieti, Italy. E-mail ppatrignani{at}unich.it

Received December 16, 2003; revision received February 3, 2004; accepted February 6, 2004.

Background— The current controversy on the potential cardioprotective effect of naproxen prompted us to evaluate the extent and duration of platelet, monocyte, and vascular cyclooxygenase (COX) inhibition by naproxen compared with low-dose aspirin.

Methods and Results— We performed a crossover, open-label study of low-dose aspirin (100 mg/d) or naproxen (500 mg BID) administered to 9 healthy subjects for 6 days. The effects on thromboxane (TX) and prostacyclin biosynthesis were assessed up to 24 hours after oral dosing. Serum TXB₂, plasma prostaglandin (PG) E₂, and urinary 11-dehydro-TXB₂ and 2,3-dinor-6-keto-PGF₁ were measured by previously validated radioimmunoassays. The administration of naproxen or aspirin caused a similar suppression of whole-blood TXB₂ production, an index of platelet COX-1 activity ex vivo, by 94±3% and 99±0.3% (mean±SD), respectively, and of the urinary excretion of 11-dehydro-TXB₂, an index of systemic biosynthesis of TXA₂ in vivo, by 85±8% and 78±7%, respectively, that persisted throughout the dosing interval. Naproxen, in contrast to aspirin, significantly reduced systemic prostacyclin biosynthesis by 77±19%, consistent with differential inhibition of monocyte COX-2 activity measured ex vivo.

Conclusions— The regular administration of naproxen 500 mg BID can mimic the antiplatelet COX-1 effect of low-dose aspirin. Naproxen, unlike aspirin, decreased prostacyclin biosynthesis in vivo.

Key Words: aspirin • naproxen • thromboxanes • epoprostenol • platelets

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