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Effects of Celecoxib, a Novel Cyclooxygenase‐2 Inhibitor, on Platelet Function in Healthy Adults: A Randomized, Controlled Trial
Author(s) -
Leese Philip T.,
Hubbard Richard C.,
Karim Aziz,
Isakson Peter C.,
Yu Shawn S.,
Geis G. Steven
Publication year - 2000
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/00912700022008766
Subject(s) - celecoxib , naproxen , cyclooxygenase , medicine , platelet , thromboxane b2 , pharmacology , bleeding time , hemostasis , thromboxane a2 , placebo , thromboxane , ex vivo , aspirin , chemistry , platelet aggregation , in vitro , enzyme , biochemistry , pathology , alternative medicine
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 but 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.