Summary
SKF 107260 is a potent pentapeptide antagonist of the platelet membrane glycoprotein
receptor GP IIb/IIIa. The in vitro platelet inhibitory effects of SKF 107260, acetylsalicylic
acid (ASA), and their combination, on collagen-induced platelet aggregation and secretion
(ATP release) were assessed in human whole blood. Additionally, the con-centration-response
relationships for these inhibitors were compared for males and females in order to
explore gender differences in platelet responsiveness. SKF 107260 caused a concentration-dependent
inhibition of platelet aggregation which was significant at concentrations ≥30 nM.
ASA also caused a concentration-dependent inhibition of platelet aggregation which
was significant at concentrations ≥ 1 mg/dl. The addition of ASA 1 mg/dl to increasing
concentrations of SKF 107260 resulted in a more pronounced inhibition of platelet
aggregation than when either agent was used alone. These data suggest a pharmacologic
interaction, especially at SKF 107260 concentrations ≤30 nM. Since ATP release was
significantly inhibited at concentrations ≥ 1 nM, platelet secretion appears to be
more sensitive than aggregation to inhibition by SKF 107260. These data suggest that
platelet secretion in response to collagen is dependent on the aggregation response
mediated by GP IIb/IIIa. In conclusion, SKF 107260 is a potent inhibitor of both whole
blood platelet aggregation and secretion and these anti-aggregatory effects may be
augmented by concomitant ASA administration.
