Effects of celecoxib, a novel cyclooxygenase-2 inhibitor, on platelet function in healthy adults: A randomized, controlled trial

Conventional nonsteroidal anti-inflammatory drugs (NSAIDs) nonspecifically inhibit cyclooxygenase-1 (COX-1), an enzyme critical to normal platelet function, and COX-2, which mediates inflammatory response mechanisms. Celecoxib, an antiarthritic agent that inhibits COX-2 brit spares COX-1 at therapeutic doses, is expected to have minimal effects on platelet function. A double-blind, randomized placebo-controlled study of 10 days' duration was conducted in 24 healthy adults to compare the effects on platelet function of a supratherapeutic dose of celecoxib: (600 mg bid) with a standard dose of naproxen (500 mg bid), a conventional NSAID. Ex vivo platelet aggregation in response to standard agonists (collagen, arachidonate, or U46619 [a thromboxane A(2) receptor agonist]), bleeding time, and serum thromboxane B-2 (TxB(2)) level were measured. Unlike celecoxib or placebo, naproxen produced statistically significant reductions in platelet aggregation and serum TxB(2) levels and increased bleeding time. The results indicate that even at supratherapeutic doses, celecoxib will not interfere with normal mechanisms of platelet aggregation and hemostasis, supporting the premise that celecoxib is COX-1 sparing relative to conventional NSAIDs. Journal of Clinical Pharmacology 2000;40:124-132 (C)2000 the American College of Clinical Pharmacology.