Clinical Pharmacology of Eptifibatide
Section snippets
Platelet Membrane GP IIb-IIIa Complex
GP IIb-IIIa belongs to a large family of receptors called integrins, which are heterodimeric cell-surface proteins that play important roles in cell adhesions.14, 21, 22, 23Unlike most integrins, GP IIb-IIIa has a narrow tissue distribution, being found only on platelets and cells of the megakaryocytic lineage. GP IIb-IIIa is the most abundant protein on the surface of platelets, with some 80,000 copies per platelet,[24]representing 1–2% of total platelet protein.[25]
As depicted in Fig. 1, GP
Development of GP IIb-IIIa Inhibitors
The first GP IIb-IIIa inhibitor to be developed and extensively evaluated clinically is abciximab (ReoPro, Centocor, Malvern, PA/Eli Lilly, Indianapolis, IN),[40]a human-murine chimeric monoclonal antibody fragment derived from the murine monoclonal antibody 7E3.[41]Abciximab is an effective blocker of GP IIb-IIIa receptor function and has demonstrated antithrombotic efficacy in advanced clinical trials.42, 43The pharmacologic profile of abciximab is reflective of its high affinity for GP
Pharmacodynamics and Pharmacokinetics of Eptifibatide
The main goal of pharmacodynamic and pharmacokinetic studies with eptifibatide has been to correlate the antiplatelet activity of eptifibatide (as measured by its ability to inhibit platelet aggregation and thrombosis) with its plasma levels. On the basis of these studies, several dosing regimens of eptifibatide have been selected, and their effect on bleeding times has been measured in order to evaluate the safety profile of this drug.
Dose Selection of Eptifibatide in the Impact II and PURSUIT Trials
The dosing regimens of eptifibatide in the pivotal IMPACT II trial were selected to achieve effective antithrombotic activity safely during the procedure and in the critical hours after PTCA. IMPACT II randomized 4,010 low- and high-risk patients scheduled to undergo percutaneous intervention to receive either a placebo or 1 of the 2 eptifibatide doses.[20]All patients in the eptifibatide arms received the same 135-μg/kg bolus, which was selected because it provided a robust and rapid
Conclusions and Prospects
The conventional approaches to the management of coronary thrombosis underlying AICS and the ischemic complications of percutaneous coronary interventions have been anticoagulation with heparin and antiplatelet therapy with aspirin. The efficacy of each of these agents, however, is limited by their relatively weak effect on platelet aggregation, a key event in the pathophysiology of ischemic heart disease. The platelet GP IIb-IIIa complex involved in the final common pathway to platelet
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2021, Current Research in ToxicologyCitation Excerpt :In patients with congestive heart failure, administration of enalapril reduced mortality significantly by improving general signs & symptoms of left and right ventricular heart failure, reduction of heart size and blood pressure (Kjekshus and Swedberg, 1989). Eptifibatide is a glycoprotein IIb/IIIa class platelet inhibiting drug used to reduce ischemic cardiac events approved by FDA for Acute Coronary Syndrome (ACS) and Percutaneous Coronary Intervention (PCI) (Phillips and Scarborough, 1997). A rupture in the atherosclerotic plaque or endothelial injury exposes the subendothelial matrix of the coronary blood vessel to the circulating platelets which in turn triggers a signaling cascade that leads to the activation of glycoprotein IIb/IIIa receptor (GpIIb/IIIa) (Sangkuhl et al., 2011).
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