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A New Cyclooxygenase‐2 Inhibitor, Rofecoxib (VIOXX®), Did Not Alter the Antiplatelet Effects of Low‐Dose Aspirin in Healthy Volunteers
Author(s) -
Greenberg Howard E.,
Gottesdiener Keith,
Huntington Martha,
Wong Peggy,
Larson Pat,
Wildonger Lynn,
Gillen Lisa,
Dorval Ellen,
Waldman Scott A.
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 - 10.1177/009127000004001224
Subject(s) - rofecoxib , aspirin , cyclooxygenase , placebo , medicine , platelet , pharmacology , thromboxane b2 , thromboxane , arachidonic acid , bleeding time , anesthesia , chemistry , platelet aggregation , biochemistry , pathology , alternative medicine , enzyme
The present study examined whether rofecoxib (VIOXX ® ), a new specific inhibitor of cyclooxygenase‐2 (COX‐2), would interfere with the desired antiplatelet effects of aspirin. Thus, the effects of rofecoxib on inhibition of ex vivo serumgenerated thromboxane B 2 (TXB 2 ) and platelet aggregation by low doses (81 mg) of aspirin were examined in healthy volunteers. This was a double‐blind, randomized, placebo‐controlled, parallel study of two treatment groups ( n = 12 per group) in which subjects received 50 mg of rofecoxib or placebo for 10 days in a blinded fashion. Subjects also received 81 mg aspirin once on each of days 4 through 10 in an open‐label fashion. Blood for measurement of serum TXB 2 production and platelet aggregation studies was collected on day 1 (prior to rofecoxib/placebo), on day 4 (prior to aspirin), and on day 10 (before and 4 hours following the seventh dose of aspirin). Platelet‐derived serum TXB 2 (COX‐1 assay) was measured in blood clotted for 1 hour at 37°C. Platelet aggregation was independently induced employing 1 mM arachidonic acid and 1 μg/mL collagen as agonists. Rofecoxib administered alone had no significant effect on serum TXB 2 production or platelet aggregation (day 4). TXB 2 production was inhibited 98.4% by aspirin coadministered with either rofecoxib or placebo (day 10). Similarly, platelet aggregation induced by arachidonic acid was inhibited 93.7% and 93.5% by aspirin coadministered with either rofecoxib or placebo, respectively (day 10). The comparable values for inhibition of collagen‐induced platelet aggregation were 86.8% and 90.8%, respectively. No important clinical or laboratory adverse experiences were observed. In conclusion, rofecoxib alone (50 mg QD for 4 days) did not inhibit serum TXB 2 production or platelet aggregation. In addition, rofecoxib (50 mg QD for 10 days) did not alter the antiplatelet effects of low‐dose aspirin (inhibition of platelet aggregation and TXB 2 production). Rofecoxib was generally well tolerated when administered alone or in combination with low‐dose aspirin .