A new cyclooxygenase-2 inhibitor, rofecoxib (VIOXX (R)), did not alter theantiplatelet effects of low-dose aspirin in healthy volunteers

The present study examined whether rofecoxib (VIOXX(R)), a new specific inh ibitor of cyclooxygenase-2 (COX-2), would interfere with the desired antipl atelet effects of aspirin. Thus, the effects of rofecoxib on inhibition of ex vivo serum-generated thromboxane B-2 (TXB2) 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 off two trea tment groups (n = 12 per group) in which subjects received 50 mg of rofecox ib or placebo for 10 days in a blinded fashion. Subjects also received BI m g aspirin once on each of days 4 through 10 in an open-label fashion. Blood for measurement of serum TXB2 production and platelet aggregation studies was collected on day 1 (prior to rofecoxib/placebo), on day 4 (prior to asp irin), and on day 10 (before and 4 hours following the seventh dose of aspi rin). Platelet-derived serum TXB2 (COX-1 assay) M as measured in blood clot ted for 1 hour at 37 degreesC. Platelet aggregation was independently induc ed employing 1 mM arachidonic acid and 1 mug/mL collagen as agonists. Rofec oxib administered alone had no significant effect on serum TXB2 production or platelet aggregation (day 4). TXB, production was inhibited 98.4% by asp irin coadministered with either rofecoxib or placebo (day 10). Similarly, p latelet 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 platele t aggregation were 86.8% and 90.8%, respectively. No important clinical or laboratory adverse experiences were observed. In conclusion, rofecoxib alon e (50 mg QD for 4 days) did nor inhibit serum TXB, production or platelet a ggregation. In addition, rofecoxib (50 mg QD for 10 days) did not alter the antiplatelet effects of low-dose aspirin (inhibition of platelet aggregati on and TXB, production). Rofecoxib was generally well tolerated when admini stered alone or in combination with low dose aspirin. (C) 2000 The American College of Clinical Pharmacology.