Clopidogrel: An Antithrombotic Drug Acting on the ADP-dependent Activation Pathway of Human Platelets

The aim of the study was to determine the effect of clopidogrel on adenosine diphosphate (ADP)- induced platelet activation in human volunteers. Platelets from human volunteers before and after a 7-day treatment with clopidogrel (75 mg/kg), were tested for their sensi tivity to ADP by measuring ADP-induced aggregation, adenylyl cyclase downregulation, and [3H]-2-MeS-ADP binding. Platelet membrane glycoprotein (GP IIb-IIIa; GP Ib, GMP-140) expression was measured by flow cy tometry using fluorescent-labeled antibodies or fibrino gen. After oral administration to human volunteers (75 mg/day for 7 days), clopidogrel, a novel ADP-selective antiplatelet agent, inhibited ADP-induced aggregation of platelets ex vivo. This effect was irreversible in nature, and no activity could be detected in the plasma of treated subjects. Although clopidogrel did not modify ADP- induced shape change, it prevented the inhibitory effect of ADP (but not that of epinephrine) on the prostoglandin- E 1 (PGE1)-induced increase in pla...