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

• Published in: Circulation (New York, N.Y.) Vol. 109; no. 12; pp. 1468 - 1471
• Main Authors: Capone, Marta L., Tacconelli, Stefania, Sciulli, Maria G., Grana, Marilena, Ricciotti, Emanuela, Minuz, Pietro, Di Gregorio, Patrizia, Merciaro, Gabriele, Patrono, Carlo, Patrignani, Paola
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 30.03.2004
• Subjects: 6-Ketoprostaglandin F1 alpha - analogs & derivatives; 6-Ketoprostaglandin F1 alpha - urine; Adult; Aspirin - administration & dosage; Aspirin - pharmacology; Biological and medical sciences; Blood and lymphatic vessels; Blood Platelets - drug effects; Blood Platelets - enzymology; Cardiology. Vascular system; Cardiotonic Agents - pharmacology; Cross-Over Studies; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors - pharmacology; Dinoprostone - blood; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Endothelial Cells - drug effects; Endothelial Cells - enzymology; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Endothelium, Vascular - enzymology; Female; Humans; Isoenzymes - antagonists & inhibitors; Isoenzymes - blood; Male; Medical sciences; Membrane Proteins; Middle Aged; Monocytes - drug effects; Monocytes - enzymology; Naproxen - pharmacology; Prostaglandin-Endoperoxide Synthases - blood; Prostaglandins I - biosynthesis; Thromboxane B2 - analogs & derivatives; Thromboxane B2 - blood; Thromboxane B2 - urine; Human; Prostaglandin-endoperoxide synthase; Monocyte; Enzyme; Arachidonic acid derivatives; Low dose; Cardiovascular disease; Acetylsalicylic acid; Epoprostenol; Platelet; Eicosanoid; Naproxen; Clinical pharmacology; Oxidoreductases; Thromboxane
• ISSN: 0009-7322; 1524-4539; 1524-4539
• DOI: 10.1161/01.CIR.0000124715.27937.78

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) E 2 , and urinary 11-dehydro-TXB 2 and 2,3-dinor-6-keto-PGF 1α were measured by previously validated radioimmunoassays. The administration of naproxen or aspirin caused a similar suppression of whole-blood TXB 2 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-TXB 2 , 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.