TICLOPIDINE AND PLATELET-FUNCTION IN HEALTHY-VOLUNTEERS

The influence of a 4-weeks therapy with 500 mg ticlopidine daily on platelet function parameters was examined in 10 male healthy volunteers aged 20-33 years in order to extend the knowledge on the antiplatelet activity of this substance. Ticlopidine significantly (p < 0.01) affected ex-vivo platelet aggregation induced by ADP and increased platelet sensitivity to the antiaggregatory action of PGI2. Generation of TXB2 from endogenous substrate during spontaneous clotting of blood (serum-TXB2), conversion of exogenous radio-labelled labelled arachidonic acid into TXB2 and MDA-formation in isolated platelets were unaffected by the treatment. The TXB2-level in plasma of volunteers, however, was decreased, after administration of the drug. The diminished alpha-granule content liberation (beta-thromboglobulin: p < 0,01; PDGF: p < 0.01; PF4 not significant) indicates that ticlopidine induces a decrease in platelet activity. The beneficial effect on release reaction is not associated with a decrease in TXA2-formation. Our results demonstrate that ticlopidine inhibits platelet activity, especially the PDGF-release. These results confirm the value of this drug in the prevention of atherosclerosis and its thromboembolic complications.