Celecoxib administration interferes with the anti‐platelet effect of low dose aspirin in canines

Abstract

The purpose of this study was to determine whether simultaneous treatment with celecoxib (CEL) interferes with the anti‐platelet effects of aspirin (ASA). Patients at risk for adverse cardiovascular events often are prescribed a low dose (81 mg) of ASA to selectively inhibit the cyclooxygenase (COX)‐1 dependent synthesis of thromboxane A2 in platelets. Many of these patients are simultaneously administered the COX‐2 specific inhibitor, CEL, for pain management. Recent in vitro reports demonstrated the ability of CEL to bind to COX‐1 thereby slowing the rate of acetylation of the critical Ser530 by ASA without otherwise affecting the ability of the enzyme to metabolize arachidonic acid (AA). Therefore, it is important to understand whether CEL might adversely affect the beneficial cardiovascular effects of ASA in vivo. To test this question, dogs were administered ASA (1.16 or 4.64 mg/kg), CEL (1.43 mg/kg, bid) or the combination of both ASA and CEL for a period of at least three days. At the conclusion of each regimen, blood was collected and ex vivo platelet aggregation responses were recorded. As expected, AA‐induced platelet aggregation was inhibited by both doses of ASA. CEL administration alone had no effect on platelet aggregation. Simultaneous administration of CEL with low dose, but not high dose ASA interfered with the inhibitory effect of ASA on platelet aggregation. The results highlight the complex function of these enzymes in the hemostatic process.