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

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 μg · mL −1 ) and SR121566A (31 and 62 ng · 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 μmol/L)‐induced aggregation in an additive manner, a supra‐additive effect was observed with collagen (2 μg · 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. (Clin Pharmacol Ther 2000;67:305–13.) Clinical Pharmacology & Therapeutics (2000) 67 , 305–313; doi: 10.1067/mcp.2000.104613