PHARMACODYNAMICS OF TICLOPIDINE - RELATION BETWEEN DOSE AND TIME OF ADMINISTRATION TO PLATELET INHIBITION

In spite of long clinical experience with ticlopidine (T) knowledge of its pharmacodynamics is limited. In this study relation between dose and time of administration of T to platelet inhibition was investigate d in 62 healthy volunteers ex vivo in whole blood and platelet rich pl asma. Gender-related sensitivity of platelets to ticlopidine was also evaluated. Inhibition of ADP-induced platelet aggregation by T, 500 mg , daily, was almost identical in both sexes. 100 mg daily did not inhi bit ADP-induced platelet aggregation even after 14 days of administrat ion. 250 mg daily induced strong inhibition on day 5 of administration comparable to the inhibition obtained with 500 mg daily dose. The ant iplatelet (ADP) effect of T (500 mg, daily) was present on day 2-3 and full inhibitory effect on day 4 of administration. T-1/2 of antiplate let (ADP) activity of T was 5.3 days and full recovery of platelets ac tivity 11-13 days. No rebound phenomenon was present. T (regardless th e dose) inhibited platelet aggregation induced by small but not high c oncentrations of collagen and was without effect on arachidonic acid-i nduced platelet aggregation. Therefore, T is not suitable for treatmen t of acute event, 250 mg daily dose should be used especially for comb ination with other drugs and 11 days washout interval seems necessary to change the treatment or to perform surgery.