Celecoxib, ibuprofen, and the antiplatelet effect of aspirin in patients with osteoarthritis and ischemic heart disease^*.

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

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 B2 (TXB2) levels, as well as platelet function. In contrast, a significant (P < .001) increase in serum TXB2 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-TXB2, 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 E2 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

CELECOXIB; IBUPROFEN; ASPIRIN; PHARMACODYNAMICS; OSTEOARTHRITIS; CORONARY disease

Clinical Pharmacology & Therapeutics, 2006, Vol 80, Issue 3, p264

0009-9236

Academic Journal

10.1016/j.clpt.2006.05.004