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 he althy male volunteers and the interaction of the glycoprotein IIb/IIIa (GPI Ib/IIIa) inhibitors abciximab and SR121566A with blood from those pretreate d 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, sub jects of both groups received the combined treatment. Blood from these subj ects was spiked with abciximab (0.5 and 1.5 mu g . mL(-1)) and SR121566A (3 1 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 (d ifference not significant), and 24.0 minutes (P < .01) for the combined tre atment. Fibrinogen binding to the platelet GPIIb/IIIa receptor was reduced for aspirin to 69% (difference not significant), to 63% for clopidogrel (di fference not significant), and to 63% for the clopidogrel plus aspirin comb ination (P < .01), CD62 expression as a marker of platelet granular secreti on was reduced to 66% by clopidogrel (P < .01) and to 41% by the combinatio n of clopidogrel and aspirin; aspirin alone had no effect, In vitro, with p retreatment with aspirin and clopidogrel, inhibitory effects of the GPIIb/I IIa inhibitors on fibrinogen binding were additive to changes observed with aspirin or clopidogrel alone. No effect on CD62 expression was observed wi th either GPIIb/IIIa inhibitor. Aspirin and clopidogrel reinforced effects of the GPIIb/IIIa inhibitors on adenosine diphosphate (5 mu mol/L)-induced aggregation in an additive manner, a supra-additive effect was observed wit h collagen (2 mu g . mL(-1))-induced aggregation. Conclusion: The augmentation of the antiaggregatory effects of GPIIb/IIIa i nhibitors by aspirin and clopidogrel and the lack of antisecretory effects of GPIIb/IIIa inhibitors may favor their combination with clopidogrel.