Effects of suprofen, an inhibitor of prostaglandin biosynthesis, on platelet function, plasma coagulation and fibrinolysis. I. In vitro experiments.

?The effects of suprofen, an inhibitor of prostaglandin biosynthesis, on human platelet function, fibrinolysis, proteolysis and coagulation in vitro were compared to those of reference compounds. Platelet aggregation induced by collagen, adrenaline and arachidonic acid was inhibited by suprofen depending on its concentration. Suprofen and indomethacin proved to have an equally inhibitory effect on platelet aggregation induced by collagen. Thrombin-induced aggregation was more inhibited by suprofen than by indomethacin. While the primary wave of A.D.P.-induced aggregation remained unchanged, the rate of disaggregation was enhanced by both compounds. Experiments on platelet factor-4 and 14C-serotonin release showed that suprofen and indomethacin reduced the platelet release reaction. Based upon results from experiments on synergism of suprofen with other compounds, on inhibition of arachidonic acid-induced platelet reactions and of prostaglandin E2-release, it is suggested that suprofen by inhibiting the prostaglandin biosynthesis in platelets also inhibits the platelet release reaction. In contrast to indomethacin and flufenamic acid, suprofen did not affect fibrinolysis or thrombin clotting activity. Tryptic proteolysis of albumin, however, was reduced by suprofen in a concentration-dependent and a substrate-competitive way. Tryptic decompisition of a synthetic substrate, on the other hand, was not reduced by either suprofen, indomethacin or flufenamic acid. These findings suggest that the observed reduction of albumin proteolysis by suprofen is related to an effect on the protein substrate rather than on the proteolytic enzyme itself.