Sulindac, a new non-steroidal anti-inflammatory agent, was investigated in parallel with ASA and indomethacin for its effects on platelet function. In vitro, in concentrations of 0.28 mM, the drug inhibited collagen-induced platelet aggregation without significantly affecting epinephrine-induced aggregation. ASA, indomethacin, and the sulfide metabolite of sulindac inhibited both collagen and epinephrine-induced aggregation. When all compounds were tested at a concentration of 0.14 mM, only sulindac did not inhibit collagen-induced release of 14C-serotonin. A randomized, double-blind trial of sulindac, ASA, and placebo demonstrated that inhibition of collagen-induced platelet aggregation by sulindac was transient, disappearing 24 hours after administration of the last dose of the drug. By contrast, inhibition by ASA persisted for more than 24 hours. Similar findings were noted in studies of platelet release of 14C-serotonin. As compared with the placebo group, the bleeding time was significantly prolonged 6 hours after ingestion of ASA but not after sulindac. Sulindac was clinically well-tolerated, while gastrointestinal complaints were common in subjects taking aspirin. Like ASA, sulindac administration caused no important changes in the clotting time, clot retraction, prothrombin time, partial thromboplastin time, or fibrinogen levels. Thus, in comparison with common anti-inflammatory drugs, sulindac is shown to be a moderate to weak inhibitor of platelet function.
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