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

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

Risultato della ricerca: Contributo in rivistaArticolo in rivista

202 Citazioni (Scopus)

Abstract

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 TXB 2, plasma prostaglandin (PG) E2, and urinary 11-dehydro-TXB2 and 2,3-dinor-6-keto-PGF1α 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 TXA 2 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.
Lingua originaleEnglish
pagine (da-a)1468-1471
Numero di pagine4
RivistaCirculation
Volume109
DOI
Stato di pubblicazionePubblicato - 2004

Keywords

  • 6-Ketoprostaglandin F1 alpha
  • Adult
  • Aspirin
  • Blood Platelets
  • Cardiology and Cardiovascular Medicine
  • Cardiotonic Agents
  • Cross-Over Studies
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Dinoprostone
  • Endothelial Cells
  • Endothelium, Vascular
  • Epoprostenol
  • Female
  • Humans
  • Isoenzymes
  • Male
  • Membrane Proteins
  • Middle Aged
  • Monocytes
  • Naproxen
  • Physiology
  • Platelets
  • Prostaglandin-Endoperoxide Synthases
  • Prostaglandins I
  • Thromboxane B2
  • Thromboxanes

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