Ex vivo/In vitro Interaction between ASA, Clopidogrel and GPIIb/IIIa-Inhibitors

Summary

We report on an in vivo interaction study between aspirin (ASA) and Clopidogrel in healthy male volunteers and on an in-vitro interaction of abciximab and the peptidomimetic GPIIb/IIIa-inhibitor SR121566A with blood from subjects of the in vivo-study. Ten healthy male volunteers were randomly assigned to two groups (N = 5). Group 1 started with ASA and group 2 with Clopidogrel. From day 4 to 8 subjects of both groups received combined treatment with ASA and Clopidogrel. Blood from volunteers was spiked with abciximab or SR121566A. Inhibitory effects of ASA and Clopidogrel on collagen- or ADP-induced platelet aggregation were not enhanced by the combination of both drugs. TRAP-induced fibrinogen binding was reduced under ASA to 69% (n.s.), and to 63% under Clopidogrel or Clopidogrel + ASA. CD62-expression was reduced to 66% by Clopidogrel (p <0.01 ), whereas ASA had no effect. A further significant reduction to 41 % (difference to clopidogrel/ASA alone p <0.01), was seen under combined treatment (day 8). ASA and Clopidogrel increased the effects of the GPIIb/IIIa-inhibitors on collagen (2 pg/ml)- and ADP (5 pM)-induced aggregation. Under treatment with ASA and Clopidogrel inhibitory effects of GPIIb/IIIa-inhibitors on fibrinogen binding were additive to changes seen with ASA/clopidogrel alone. No additional effect on CD62 was seen with either GPIIb/IIIa-inhibitor.

Keywords

Acetylsalicylic acid - GPIIb/IIIa-Inhibitor

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