Pharmacokinetic and pharmacodynamic effects of elinogrel: results of the platelet function substudy from the intravenous and oral administration of elinogrel to evaluate tolerability and efficacy in nonurgent percutaneous coronary intervention patients (I Elinogrel is the only selective, competitive and reversible platelet P2Y(12) inhibitor available in both intravenous (IV) and oral formulations. This substudy of the Intravenous and Oral Administration of Elinogrel to Evaluate Tolerability and Efficacy in Nonurgent Percutaneous Coronary Intervention patients (INNOVATE-PCI) trial evaluated the pharmacokinetic and pharmacodynamic effects of two dosing regimens of IV followed by oral elinogrel (120 mg IV plus 100 mg oral twice daily; 120 mg IV plus 150 mg oral twice daily) versus standard
A randomized, double-blind, active-controlled phase 2 trial to evaluate a novel selective and reversible intravenous and oral P2Y12 inhibitor elinogrel versus clopidogrel in patients undergoing nonurgent percutaneous coronary intervention: the INNOVATE-PC We evaluated the safety, efficacy, and tolerability of elinogrel, a competitive, reversible intravenous and oral P2Y(12) inhibitor that does not require metabolic activation, in patients undergoing nonurgent percutaneous coronary intervention. In a randomized, double-blind, dose-ranging phase 2b trial, 652 patients received either 300 or 600 mg of clopidogrel pre-percutaneous coronary intervention followed by 75 mg daily or 80 or 120 mg of IV elinogrel followed by 50, 100, or 150 mg oral elinogrel twice daily. Numerous exploratory safety
Viewpoint: reversible nature of platelet binding causing transfusion-related acute lung injury (TRALI) syndrome may explain dyspnea after ticagrelor and elinogrel. There may be a universal mechanism explaining dyspnea after ticagrelor and elinogrel, namely, transfusion-related acute lung injury (TRALI). Indeed, recent clinical trials with ticagrelor (DISPERSE, DISPERSE-II, and PLATO ), and elinogrel (INNOVATE PCI) revealed double-digit rates of dyspnea after novel reversible antiplatelet agents. In contrast, dyspnea is not associated with conventional non-reversible agents such as aspirin, or thienopyridines (ticlopidine, clopidogrel, or prasugrel) suggesting distinct mechanism of shortness of breath after ticagrelor and elinogrel. The adenosine hypothesis has been offered to explain
in excessive CABG-related bleedingor ischemic events between cangrelor and placebo wasreported[36].Another novel P2Y12 receptor antagonist in develop-ment is elinogrel, a first in class sulfonylurea. Elinogrel isa direct-acting, reversible, and competitive antagonistthat is being developed for both intravenous and oral012345678Days following ASA ingestion0246810121416Template bleeding time (min)Fig 1. Template bleeding after ingestion of 360 mg aspirin (ASA) in7 normal volunteers. (Reprinted with permission from Ferraris, et al,Int J Angiol 2011;20:1-18[7].)1765Ann Thorac SurgUPDATE TO STS PRACTICE GUIDELINEFERRARIS ET AL2012;94:1761– 81ANTIPLATELET DRUGS IN CARDIAC AND NONCARDIAC OPERATIONSREPORTadministration[37]. The manufacturers of elinogrel ex-pect to begin phase
A Comparative Study of Molecular Structure, pKa, Lipophilicity, Solubility, Absorption and Polar Surface Area of Some Antiplatelet Drugs Theoretical chemistry methods have been used to study the molecular properties of antiplatelet agents (ticlopidine, clopidogrel, prasugrel, elinogrel, ticagrelor and cangrelor) and several thiol-containing active metabolites. The geometries and energies of most stable conformers of these drugs have been computed at the Becke3LYP/6-311++G(d,p) level of density functional theory. Computed dissociation constants show that the active metabolites of prodrugs (ticlopidine, clopidogrel and prasugrel) and drugs elinogrel and cangrelor are completely ionized at pH 7.4. Both ticagrelor and its active metabolite are present at pH = 7.4 in neutral undissociated form
because it has been reported that this symptom occurs more frequently with the administration of the new oral reversibly-binding platelet P2Y12 receptor inhibitors ticagrelor [1-6], cangrelor [7-10], and elinogrel [11]. This paper succinctly addresses the current understanding of the pathophysiology, clinical presentation, and diagnostics of dyspnea, associated either with bronchopulmonary function
(i.e. stable CAD vs. ACS).• Randomized trials of intravenous P2Y12 inhibitors, ticlopidine, cilostazol, dypiridamole, and investigational P2Y12 inhibitors (e.g. elinogrel).Main outcome(s)The following outcome measures will be tried to be extracted from the studies that meet the eligibility criteria:Severe bleeding (TIMI minor or major, or BARC 3 or 5)MACE (composite of cardiovascular death, MI
that inhibition of P2Y12 on sensory neurons increases the sensation of dyspnea, particularly when reversible inhibitors are used. We base our hypothesis on the following considerations: 1) cangrelor and elinogrel, which, like ticagrelor, are reversible P2Y12 inhibitors, also increase the incidence of dyspnea; 2) it is biologically plausible that inhibition of P2Y12 on sensory neurons increases the sensation
Rationale and design of the randomized, double-blind trial testing INtraveNous and Oral administration of elinogrel, a selective and reversible P2Y(12)-receptor inhibitor, versus clopidogrel to eVAluate Tolerability and Efficacy in nonurgent Percutaneous Despite current dual-antiplatelet therapy with aspirin and clopidogrel, adverse clinical events continue to occur during and after percutaneous or emergency surgery. Novel antiplatelet agents are required to improve management of patients undergoing PCI. Elinogrel is a potent, direct-acting (ie, non-prodrug), selective, competitive, and reversible P2Y(12) inhibitor available in both intravenous and oral formulations. The INNOVATE-PCI study is a phase 2 randomized, double-blind, clopidogrel-controlled trial to evaluate the safety, tolerability
Safety and feasibility of adjunctive antiplatelet therapy with intravenous elinogrel, a direct-acting and reversible P2Y12 ADP-receptor antagonist, before primary percutaneous intervention in patients with ST-elevation myocardial infarction: the Early Rap Inhibition of the P2Y12 ADP-receptor with oral antiplatelet agents given to patients undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) is associated with improved outcomes, but this strategy is limited by the time required for maximal antiplatelet effect after administration. We examined the safety and tolerability of a novel, direct-acting, reversible, intravenous P2Y12 ADP-receptor antagonist, elinogrel, versus placebo when administered to STEMI patients before primary PCI
and two additional sub-studies, loading dose 180mg and maintenance dose 90mg twice daily) and elinogrel (one study; bolus range 10mg to 60mg). The loading dose of clopidogrel ranged from 300mg to 600mg and, where reported, long-term dosage was 75mg