Time and dose dependent augmentation of inhibitory effects of abciximab by aspirin.
Aspirin and abciximab independently decrease the incidence of cardiac events. To identify potential interactions, antiplatelet effects of abciximab were characterized in blood from healthy subjects given aspirin. Platelet activation was determined in whole blood with and without abciximab (2 microg/ml) added in vitro. Flow cytometry was used to quantify fibrinogen binding (glycoprotein IIb-IIIa activation). Binding of fluorochrome-labeled and 125I-labeled abciximab was determined before and after exposure to aspirin. In blood from subjects given aspirin for 5 days, abciximab-induced inhibition of the capacity to bind fibrinogen in response to 1 microM ADP was greater when the daily dose had been 325 mg compared with 81 mg (% inhibition: no aspirin 53 +/- 6; 81 mg daily 62 +/- 5; 325 mg daily 69 +/- 6). The effect of 5 daily doses of aspirin was greater than that of one. Larger single doses elicited larger effects (% inhibition 2 h after 325 mg 59 +/- 6; 2 h after 650 mg 78 +/- 5). Neither salicylsalicylic acid nor naproxen sodium potentiated the effect of abciximab. Exposure of platelets to 14C-acetylsalicylic acid led to acetylation of glycoprotein IIb and IIIa. Binding of 125I-abciximab to platelets was increased after 30 and 60 min. Acetylation of glycoprotein IIb-IIIa by aspirin augments inhibitory effects of abciximab in a dose- and time-dependent manner by increasing binding of abciximab to platelets.
Department of Medicine, University of Vermont, Burlington 05446, USA. djschnei@zoo.uvm.edu
D J
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Schneider
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Baumann
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MB
Holmes
D J
DJ
Taatjes
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Sobel
D000077284:Abciximab; D000107:Acetylation; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000494:pharmacology*; D001241:Aspirin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D002250:Carbon Radioisotopes; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology; D010979:Platelet Function Tests; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D013997:Time Factors
D000911:Antibodies, Monoclonal; D002250:Carbon Radioisotopes; D007140:Immunoglobulin Fab Fragments; D007457:Iodine Radioisotopes; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D005340:Fibrinogen; D001241:Aspirin; D000077284:Abciximab