No evidence for an influence of the human platelet antigen-1 polymorphism on the antiplatelet effects of glycoprotein IIb/IIIa inhibitors.
This study investigated the hypothesis that the human platelet antigen-1 (HPA-1) polymorphism may influence the antiplatelet effects of glycoprotein (GP)IIb/IIIa inhibitors. Adenosine diphosphate (30 micro mol)-induced fibrinogen binding was measured by flow cytometry. Abciximab (0.03-3 micro g/ml), tirofiban (0.3-30 nmol/l) or eptifibatide (0.01-1 micro g/ml) were incubated for 15 min with the samples prior to stimulation. IC(50) values for the inhibition of fibrinogen binding were determined from each experiment. All subjects were genotyped by GALIOS and automated fluorescence correlation spectroscopy. Although a marked variability in the inhibitory effects of all three GPIIb/IIIa inhibitors was confirmed, there were no significant differences between the genotypes with respect to the inhibition of fibrinogen binding. Thus, the present study does not provide evidence for an effect of HPA-1 polymorphism on the inter-individual variability in the platelet inhibitory effects of the three GPIIb/IIIa inhibitors approved for clinical use.
D000077284:Abciximab; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D016824:Antigens, Human Platelet / Q000235:genetics*; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D005340:Fibrinogen / Q000378:metabolism; D005838:Genotype; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D039661:Integrin beta3; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011110:Polymorphism, Genetic; D000077466:Tirofiban; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D016824:Antigens, Human Platelet; C061248:ITGB3 protein, human; D007140:Immunoglobulin Fab Fragments; D039661:Integrin beta3; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D014443:Tyrosine; D000244:Adenosine Diphosphate; D005340:Fibrinogen; D000077466:Tirofiban; D000077284:Abciximab