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  • Title: Pharmacodynamics of ticlopidine: relation between dose and time of administration to platelet inhibition.
    Author: Kuzniar J, Splawinska B, Malinga K, Mazurek AP, Splawinski J.
    Journal: Int J Clin Pharmacol Ther; 1996 Aug; 34(8):357-61. PubMed ID: 8864800.
    Abstract:
    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 investigated in 62 healthy volunteers ex vivo in whole blood and platelet rich plasma. 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 inhibit ADP-induced platelet aggregation even after 14 days of administration. 250 mg daily induced strong inhibition on day 5 of administration comparable to the inhibition obtained with 500 mg daily dose. The antiplatelet (ADP) effect of T (500 mg, daily) was present on day 2-3 and full inhibitory effect on day 4 of administration. T1/2 of antiplatelet (ADP) activity of T was 5.3 days and full recovery of platelets activity 11-13 days. No rebound phenomenon was present. T (regardless the dose) inhibited platelet aggregation induced by small but not high concentrations of collagen and was without effect on arachidonic acid-induced platelet aggregation. Therefore, T is not suitable for treatment of acute event, 250 mg daily dose should be used especially for combination with other drugs and 11 days washout interval seems necessary to change the treatment or to perform surgery.
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