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Antiplatelet characteristics of Z4A5, a novel selective platelet glycoprotein IIb/IIIa inhibitor, under long‐term infusion (837.13)

Introduction:Glycoprotein IIb/IIIa inhibitors are important in the treatment of acute coronary syndromes (ACS) and percutaneous coronary interventions due to their effects on the final common pathway of platelet aggregation. Z4A5 is a new hexapeptide IIb/IIIa inhibitor with antiplatelet and antithrombotic effects. This study was performed to assess the stability of the antiplatelet effects and characteristics of Z4A5 with long‐term infusion. Materials and Methods:Light‐transmission aggregometry was used to measure platelet aggregation to assess the antiplatelet efficacy of Z4A5 in vitro and ex vivo. The activity of Z4A5against platelet aggregation and template bleeding time were evaluated after 8‐hour intravenous infusions in Beagle dogs following a 3 × 3 Latin square design. The recovery of platelet function after suppression by Z4A5 was compared with the recovery following eptifibatide and tirofiban administration 4h after termination. Results:Z4A5 completely inhibited Adenosine diphosphate (ADP)‐ and thrombin‐induced in vitro platelet aggregation with an IC50 of 265.8±22.9 nM and 180.3±58.2 nM. It also markedly and stably prevented ADP‐induced ex vivo platelet aggregation and prolonged the bleeding time throughout the 8‐hour infusion. Platelet function suppressed by long‐term infusion of Z4A5 recovered significantly faster than after eptifibatide infusion.Conclusions: Z4A5 has a stable antiplatelet effect and can be more readily controlled by physicians to monitor platelet function in ACS patients compared with two other GP IIb/IIIa inhibitors.