EFFECTS OF TICLOPIDINE ADMINISTERED TO HEALTHY-VOLUNTEERS ON PLATELET-FUNCTION IN WHOLE-BLOOD

Ticlopidine is thought to be a selective inhibitor of ADP-induced plat elet function. Here we have investigated the effects of ticlopidine on platelet function in whole blood induced by ADP and by other platelet agonists. Whole blood was used because it was considered that ADP der ived from led cells might act synergistically with other platelet agon ists to enhance platelet responses, and that ticlopidine might interfe re with this process. Measurements were performed using blood from 16 healthy volunteers before ticlopidine administration, after taking tic lopidine 250 mg daily for 10 days, after taking ticlopidine 250 mg twi ce daily for a further 10 days, and after 14 days off treatment. Ticlo pidine proved to be a very effective inhibitor of the platelet aggrega tion induced by ADP; it was most effective in enhancing the reversibil ity of the aggregation response. The drug modestly but significantly r educed streptokinase, adrenaline, collagen, sodium arachidonate, PAF a nd U46619 - induced platelet aggregation. The drug significantly reduc ed the extent of the release reaction (C-14-5HT release) induced by AD P, streptokinase, PAF, ristocetin and sodium arachidonate, and also re duced the extent of the synergistic C-14-5HT release induced by combin ations of ADP and PAF, ADP and adrenaline and PAF and adrenaline. The various inhibitory effects of ticlopidine were evident after treatment with 250 mg daily but were more pronounced after 250 mg tn ice daily. AU values had returned to normal after 14 days off treatment. Ticlopi dine had no effect on serum thromboxane B-2 production nor an several parameters of coagulation and fibrinolysis. We conclude that ticlopidi ne is an effective inhibitor of ADP-induced platelet aggregation and a lso the platelet aggregation and C-14-5HT release induced in whole blo od by a number of platelet agonists and combinations of agonists. Thes e latter effects are probably mainly via a selective effect on ADP. Th e inhibitory effects of the drug are dose-related.