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  • Title: Ex vivo--in vitro interaction between aspirin, clopidogrel, and the glycoprotein IIb/IIIa inhibitors abciximab and SR121566A.
    Author: Klinkhardt U, Kirchmaier CM, Westrup D, Graff J, Mahnel R, Breddin HK, Harder S.
    Journal: Clin Pharmacol Ther; 2000 Mar; 67(3):305-13. PubMed ID: 10741635.
    Abstract:
    OBJECTIVES: 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). METHODS: 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)). RESULTS: 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. CONCLUSION: 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.
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