Effect of acetylsalicylic acid on inhibition of ex vivo platelet aggregation and secretion by SKF 107260, a novel GPIIb/IIIa receptor antagonist.
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 concentration-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 > or = 30 nM. ASA also caused a concentration-dependent inhibition of platelet aggregation which was significant at concentrations > or = 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 < or = 30 nM. Since ATP release was significantly inhibited at concentrations > or = 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.
Freed
M I
MI
SmithKline Beecham Clinical Research Unit, Presbyterian Medical Center of Philadelphia, PA 19104.
Boike
S
S
Zariffa
N
N
Jorkasky
D K
DK
D000255:Adenosine Triphosphate / Q000097:blood / Q000378:metabolism*; D000328:Adult; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D003094:Collagen / Q000494:pharmacology; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D012727:Sex Characteristics
D010456:Peptides, Cyclic; D010980:Platelet Membrane Glycoproteins; C086543:SK&F 107260; D000255:Adenosine Triphosphate; D003094:Collagen; D001241:Aspirin