Inhibitory effect of TN-762 (suprofen) on the platelet aggregation

Inhibitory effects of TN-762 (suprofen), ketoprofen, and indomethacin on rat or rabbit platelet aggregation were examined. Of these compounds tested, suprofen showed the most potent effect on platelet aggregation in vitro, especially in AA-induced rabbit platelet aggregation (IC50=0.01 μM). Suprofen showed an inhibitory effect similar to that of ketoprofen and indomethacin on rat platelet aggregation ex vivo. The lethal effect of AA in the rabbits was protected by suprofen (0.05 mg/kg p.o.) at concentrations lower than the other compounds. Similar to the other compounds, suprofen had little effect on the PG I2 synthesis in the rat aorta. In order to test the direct effects of these compounds on the platelet avoiding the effects of other plasma components, gel-filtrated rat platelets were used. All tested compounds showed similar inhibitory effect. To investigate the interaction of these compounds with the lipid bilayers, we used the liposome as a model membrane. The tested compounds inhibited liposome aggregation induced by 4 mM Ca2+. In this experiment, the interaction of suprofen with the lipid bilayers was shown.