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Celecoxib, ibuprofen, and the antiplatelet effect of aspirin in patients with osteoarthritis and ischemic heart disease
Author(s) -
Renda Giulia,
Tacconelli Stefania,
Capone Marta L.,
Sacchetta Daniele,
Santarelli Francesco,
Sciulli Maria G.,
Zimarino Marco,
Grana Marilena,
D'Amelio Elisabetta,
Zurro Maria,
Price Thomas S.,
Patrono Carlo,
De Caterina Raffaele,
Patrignani Paola
Publication year - 2006
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2006.05.004
Subject(s) - celecoxib , aspirin , medicine , cyclooxygenase , ibuprofen , thromboxane b2 , thromboxane , platelet , arachidonic acid , pharmacology , placebo , platelet activation , chemistry , biochemistry , alternative medicine , pathology , enzyme
Background and Objective We performed a placebo‐controlled, randomized study to address whether celecoxib or ibuprofen undermines the functional range of inhibition of platelet cyclooxygenase (COX)–1 activity by aspirin in patients with osteoarthritis and stable ischemic heart disease. Methods Twenty‐four patients who were undergoing long‐term treatment with aspirin (100 mg daily) for cardioprotection were coadministered celecoxib, 200 mg twice daily, ibuprofen, 600 mg 3 times daily, or placebo for 7 days. Results The coadministration of placebo or celecoxib did not undermine the aspirin‐related inhibition of platelet COX‐1 activity, as assessed by measurements of serum thromboxane B 2 (TXB 2 ) levels, as well as platelet function. In contrast, a significant ( P < .001) increase in serum TXB 2 level was detected on day 7 before drug administration (median, 19.13 ng/mL [range, 1–47.5 ng/mL]) and at 24 hours after the coadministration of aspirin and ibuprofen (median, 22.28 ng/mL [range, 4.9–44.4 ng/mL]) versus baseline (median, 1.65 ng/mL [range, 0.55–79.8 ng/mL]); this was associated with a significant increase in arachidonic acid‐induced platelet aggregation ( P < .01) and adenosine diphosphate‐induced platelet aggregation ( P < .05) and a decrease in the time to form an occlusive thrombus in the platelet function analyzer ( P < .01). The urinary excretion of 11‐dehydro‐TXB 2 , an index of systemic thromboxane biosynthesis, was not significantly affected by the coadministration of treatment drugs. At steady state, a comparable and persistent inhibition of lipopolysaccharide‐stimulated prostaglandin E 2 generation, a marker of COX‐2 activity ex vivo, was caused by ibuprofen (≥80%) or celecoxib (≥70%) but not placebo. Conclusions Unlike ibuprofen, celecoxib did not interfere with the inhibition of platelet COX‐1 activity and function by aspirin despite a comparable suppression of COX‐2 ex vivo in patients with osteoarthritis and stable ischemic heart disease. Clinical Pharmacology & Therapeutics (2006) 80 , 264–274; doi: 10.1016/j.clpt.2006.05.004