INVITRO AND EXVIVO EFFECTS OF INDOBUFEN ON HUMAN-PLATELET AGGREGATION, THE RELEASE REACTION AND THROMBOXANE-B2 PRODUCTION

We have done a comprehensive study in normal volunteers of the in vitro and ex vivo effects of the antiplatlet agent indobufen on platelet aggregation, the release reaction and thromboxane B2 (TxB2) production as induced by different concentrations of aggregating agents. At low concentrations (10 μM), indobufen completely inhibited secondary platelet aggregation, the release reaction and TxB2 production stimulated by ADP, epinephrine and low concentrations of platelet-activating factor (PAF acether). Higher concentrations of indobufen (100 μM) completely inhibited TxB2 production, platelet aggregation and ATP release induced by arachidonic acid (1 mM) or collagen (2 μg/ml) . The inhibitory effect was partially overcome by higher concentrations of arachidonic acid (2 mM). Data obtained ex vivo 2 h after the oral administration of 200 mg indobufen to 8 normal volunteers were in keeping with those of the in vitro study. We concluce that indobufen inhibits platelet aggregation and the release reaction by inhibiting the platelet arachidonate pathway.