Platelet glycoprotein IIb/IIIa blockade with tirofiban: effect on aggregation caused by P256, an antibody to human IIb/IIIa receptors.
OBJECTIVE
P256 is a divalent antibody which aggregates human platelets by interaction with glycoprotein (GP) IIb/IIIa receptors. We investigated the effect of tirofiban, an antagonist of the GP IIb/IIIa receptor, on P256-mediated platelet aggregation.


METHODS
Responses to agonists were measured turbidometrically at 37 degrees C in stirred citrated platelet-rich plasma from venous blood samples from healthy human volunteers. Inhibitory effects were determined by comparison with aggregation to the same concentration of agonist in a vehicle treated sample.


RESULTS
Tirofiban inhibited a near maximally effective dose of P256 (10-7 mol l-1 ) with an IC50 of 9. 3x10-8 mol l-1. Tirofiban (10-7 mol l-1 ) inhibited responses to arachidonic acid, U46619 and P256 similarly, whereas aspirin (1. 1x10-4 mol l-1 ) inhibited arachidonic acid more effectively than P256 (P<0.007 by anova ).


CONCLUSIONS
Tirofiban potently and selectively inhibits P256-stimulated aggregation of human platelets.
Merck Sharp and Dohme, Hoddesdon, Herts EN11 9BU, UK.
I
I
Fisher
P
P
Robinson
J M
JM
Ritter
D000077284:Abciximab; D019138:Antibodies, Blocking / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D016718:Arachidonic Acid / Q000494:pharmacology; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D000077466:Tirofiban; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D016718:Arachidonic Acid; D014443:Tyrosine; D000077466:Tirofiban; D000077284:Abciximab