Ex vivo--in vitro interaction between aspirin, clopidogrel, and the glycoprotein IIb/IIIa inhibitors abciximab and SR121566A

• Published in: Clinical pharmacology and therapeutics Vol. 67; no. 3; p. 305
• Main Authors: Klinkhardt, U, Kirchmaier, C M, Westrup, D, Graff, J, Mahnel, R, Breddin, H K, Harder, S
• Format: Journal Article
• Language: English
• Published: United States 01.03.2000
• Subjects: Administration, Oral; Adult; Analysis of Variance; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - pharmacology; Aspirin - administration & dosage; Aspirin - pharmacology; Benzylamines; Bleeding Time; Drug Administration Schedule; Drug Interactions; Fibrinogen - drug effects; Fibrinogen - metabolism; Humans; Immunoglobulin Fab Fragments - administration & dosage; Immunoglobulin Fab Fragments - pharmacology; Male; Nephelometry and Turbidimetry; P-Selectin - drug effects; P-Selectin - metabolism; Piperidines; Platelet Aggregation Inhibitors - administration & dosage; Platelet Aggregation Inhibitors - pharmacology; Platelet Glycoprotein GPIIb-IIIa Complex - administration & dosage; Platelet Glycoprotein GPIIb-IIIa Complex - pharmacology; Reference Values; Thiazoles; Ticlopidine - administration & dosage; Ticlopidine - analogs & derivatives; Ticlopidine - pharmacology
• ISSN: 0009-9236
• DOI: 10.1067/mcp.2000.104613

To assess the interaction between aspirin and clopidogrel in healthy male volunteers and the interaction of the glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitors abciximab and SR121566A with blood from those pretreated subjects (ex vivo-in vitro). Aspirin (300 mg/day), clopidogrel (75 mg/day), or the combination of both drugs were administered orally for 8 days. Group 1 (n = 5) started with aspirin and group 2 (n = 5) with clopidogrel. From day 4 to day 8, subjects of both groups received the combined treatment. Blood from these subjects was spiked with abciximab (0.5 and 1.5 microg x mL(-1)) and SR121566A (31 and 62 ng x mL(-1)). In vivo, average bleeding times were 6.8 minutes at baseline, 20.3 minutes for clopidogrel alone (P < .01), 10.9 minutes for aspirin alone (difference not significant), and 24.0 minutes (P < .01) for the combined treatment. Fibrinogen binding to the platelet GPIIb/IIIa receptor was reduced for aspirin to 69% (difference not significant), to 63% for clopidogrel (difference not significant), and to 63% for the clopidogrel plus aspirin combination (P < .01). CD62 expression as a marker of platelet granular secretion was reduced to 66% by clopidogrel (P < .01) and to 41% by the combination of clopidogrel and aspirin; aspirin alone had no effect. In vitro, with pretreatment with aspirin and clopidogrel, inhibitory effects of the GPIIb/IIIa inhibitors on fibrinogen binding were additive to changes observed with aspirin or clopidogrel alone. No effect on CD62 expression was observed with either GPIIb/IIIa inhibitor. Aspirin and clopidogrel reinforced effects of the GPIIb/IIIa inhibitors on adenosine diphosphate (5 micromol/L)-induced aggregation in an additive manner, a supra-additive effect was observed with collagen (2 microg x mL(-1))-induced aggregation. The augmentation of the antiaggregatory effects of GPIIb/IIIa inhibitors by aspirin and clopidogrel and the lack of antisecretory effects of GPIIb/IIIa inhibitors may favor their combination with clopidogrel.