COMPARED EFFECTS OF 3 DOSE-LEVELS OF TICLOPIDINE ON PLATELET-FUNCTION IN NORMAL SUBJECTS

The compared inhibitory effects of 3 dose-levels of ticlopidine (300, 600 and 750 mg/day) on platelet function were studied in a placebo controlled study. Ticlopidine exerted several significant effects, namely lengthening of bleeding time (300 mg/day), reduction of platelet retention on a glass-bead column (300 mg/day), reduction of the rate and the maximum extent of aggregation induced by ADP 2 .mu.M (300 mg/day) and 5 .mu.M (300 mg/day). The aggregating effects of ADP 5 .mu.M were followed by subsequent deaggregation, of which the rate was significantly increased after administration of the product (300 mg/day). Ticlopidine also significantly inhibited the release of serotonin [5-HT] (as measured by 14C-5-HT) occurring during ADP 5 .mu.M induced aggregation (300 mg/day). Epinephrine-induced aggregation (5 .mu.M) was inhibited by ticlopidine, but this effect was apparent on the 1st wave of aggregation only after 750 mg/day. The maximal rate and aggregation of the 2nd wave of epinephrine-induced aggregation were significantly inhibited after the administration of the product (300 mg/day). Ticlopidine abolished the release of 14C-5-HT induced by 5 .mu.M epinephrine but it was not possible to evaluate this effect statistically. No obvious effect was evidenced on the parameters of collagen-induced aggregation except a slight inhibition on release of 14C-5-HT. The effectiveness of ticlopidine as an antiaggregant was demonstrated. Regression lines were determined to show the correlation between the administered dose and these inhibitory effects. Even the lowest dose of 300 mg/day, which produced a moderate increase in bleeding time, significantly inhibited most of the parameters studied.