The effects of two synthetic glycoprotein IIb/IIIa antagonists, Ro 43-8857 and L-700,462, on platelet aggregation and bleeding in guinea-pigs and dogs: evidence that Ro 43-8857 is orally active.

In vitro platelet aggregation studies in whole blood were used to define the species-specificity profile of two synthetic GP-IIb/ IIIa antagonists, Ro 43-8857 and L-700,462. Aggregation of rhesus monkey platelets was inhibited with a similar potency to human platelets, whereas both compounds were poor antagonists in mini-pig, rabbit or hamster blood. Compared to human platelets, Ro 43-8857 was 2-3-fold less active as an inhibitor of dog and guinea-pig platelet aggregation, whereas L-700,462 was, respectively, 4- and 14-fold less active in these species. In vivo investigations with these two compounds were performed in anesthetized guinea-pigs and conscious dogs, with bleeding times measured on small mesenteric arteries or on the inner jowl respectively