Activated platelet glycoprotein IIb/IIIa receptor (competitive antagonist) [1]
Dissociation constant (KD) = 120 nmol/L [1]
IC50 (low extracellular ionized calcium 40-50 μmol/L) = 100 nmol/L; IC50 (physiological ionized calcium 1.1 mmol/L) = 500 nmol/L [1]
IC50 (citrated blood, ADP-induced aggregation) = 140 ± 40 nmol/L; IC50 (PPACK blood, ADP-induced aggregation) = 570 ± 70 nmol/L [1]
IC50 (citrated blood, TRAP-induced aggregation) = 170 ± 40 nmol/L; IC50 (PPACK blood, TRAP-induced aggregation) = 1190 ± 260 nmol/L [1]
Receptor occupancy IC50 (citrated blood) = 105 ± 5 nmol/L; Receptor occupancy IC50 (PPACK blood) = 420 ± 37 nmol/L [1]

Eptifibatide is a cyclic heptapeptide with antiplatelet properties that functions as a competitive antagonist of activated platelet glycoprotein IIb/IIIa receptors [1].

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Eptifibatide binds rapidly to platelet binding sites, achieving full platelet inhibition within 15 minutes [1].
Approximately 25% of eptifibatide is protein-bound under physiological conditions, while the remainder remains free and pharmacologically active in the circulation [1].
In the PRIDE trial, using PPACK-anticoagulated blood samples and stimulation with 20 μmol/L ADP, the IMPACT II dose regimen (135 μg/kg bolus + 0.75 μg/kg/min infusion) failed to maintain at least 80% platelet inhibition. Higher-dose regimens (180 μg/kg bolus + 2 μg/kg/min infusion, or 250 μg/kg bolus + 3 μg/kg/min infusion) maintained >80% inhibition, with very profound inhibition in the highest dose group [1].
The steady-state eptifibatide concentration threshold required to achieve a goal of 80% receptor occupancy was 1650 μg/L (95% CI 1406–1967 μg/L) [1].
In the PERIGEE substudy, the 180 μg/kg bolus with 2 μg/kg/min infusion produced target level of platelet inhibition (>80%) in >80% of patients during the whole 72-hour treatment period, using PPACK-anticoagulated blood and stimulation with ADP or TRAP [1].
In the PRIDE substudy, double-bolus regimens achieved >90% inhibition of platelet aggregation to 20 μmol/L ADP in most patients across all groups by 1 hour, overcoming the partial recovery of platelet function seen in single-bolus groups [1].

In the IMPACT II phase III trial (4010 patients undergoing PCI), eptifibatide regimens (135 μg/kg bolus + 0.5 or 0.75 μg/kg/min infusion for 20-24h) showed a treatment effect but it was not statistically significant on intention-to-treat analysis. Primary endpoint incidence: placebo 11.4%, lower-dose 9.2%, higher-dose 9.9% [1].
In the PURSUIT trial (10,948 patients with acute coronary syndromes), eptifibatide (180 μg/kg bolus + 2 μg/kg/min infusion for up to 72h) caused a 1.5% absolute reduction in the primary efficacy endpoint (death or nonfatal myocardial infarction at 30 days: eptifibatide 14.2%, placebo 15.7%; p=0.04) [1].
In the ESPRIT trial (2064 patients undergoing elective stent PCI), eptifibatide (two 180 μg/kg boluses 10 minutes apart + 2 μg/kg/min infusion for 16-24h) showed a 43% relative risk reduction in the irreversible endpoints of death or myocardial infarction at 48 hours (95% CI 19-61%, p=0.0017). The primary composite endpoint at 30 days (death, myocardial infarction, or revascularization) was reduced from 22.1% in placebo to 17.5% in eptifibatide (hazard ratio 0.76, 95% CI 0.63-0.93; p=0.007) [1].

Platelet aggregation was measured using light transmittance aggregometry on platelet-rich plasma (PRP) samples. PRP was anticoagulated either with 3.8% sodium citrate (which chelates ionized calcium, resulting in effective calcium concentrations of 40-50 μmol/L) or with PPACK (Phe-Pro-Arg-chloromethyl ketone, which does not alter calcium concentrations). Platelets were then stimulated with 20 μmol/L adenosine diphosphate (ADP) or thrombin receptor agonist peptide (TRAP) to induce aggregation in the presence of different concentrations of eptifibatide. The concentration required to inhibit aggregation by 50% (IC50) was determined [1].
Receptor occupancy was quantified using a GPIIb/IIIa-specific antibody and a fluorescence technique that detects the receptor bound by the antagonist [1].
In the PRIDE trial, platelet aggregation studies stimulated by 20 μmol/L ADP were measured on PRP samples anticoagulated with the non-chelating agent PPACK [1].
In the PERIGEE substudy, blood was anticoagulated with either citrate or PPACK, and platelet aggregation was tested using standard aggregometry with stimulation by both TRAP and ADP [1].

Blood samples collected from patients were anticoagulated with citrate or PPACK. Platelet-rich plasma (PRP) was prepared, and platelets were challenged with 20 μmol/L ADP or TRAP to induce aggregation. Platelet aggregation was measured using light transmittance aggregometry. The effect of eptifibatide on platelet inhibition was assessed by comparing aggregation in the presence of various concentrations of eptifibatide. The use of citrate (calcium-chelating anticoagulant) resulted in apparently enhanced eptifibatide-induced platelet inhibition compared to PPACK (non-chelating anticoagulant) [1].
In the PRIDE substudy, serial blood samples anticoagulated with PPACK were drawn for platelet aggregation, GPIIb/IIIa receptor occupancy, and eptifibatide serum concentrations. Bleeding times were also measured and returned to ≤30 minutes in all groups within 4 hours of termination of infusion [1].

Absorption, Distribution and Excretion
55 mL/kg/h [Patients with Coronary Artery Disease] / Breast Milk / It is unclear whether epitubatide is distributed in human breast milk. epitubatide binds to plasma proteins at a rate of approximately 25%, primarily albumin (9-16%). The volume of distribution of epitubatide in patients with coronary artery disease is approximately 185-260 mL/kg, while the volume of distribution in healthy individuals is slightly higher (220-270 mL/kg). epitubatide is a synthetic platelet glycoprotein IIb/IIIa receptor inhibitor that has been investigated as an antithrombotic agent for various acute ischemic coronary syndromes. This study aimed to characterize the distribution of (14)C-epitubatide in humans following a single intravenous (iv) bolus dose. (14)C-epitubatide (approximately 50 μCi) was administered to eight healthy men at a single intravenous bolus dose of 135 μg/kg. Blood, exhaled carbon dioxide, urine, and fecal samples were collected within 72 hours after administration, and their radioactivity was analyzed using liquid scintillation counting. Simultaneously, epitubatin and its deamide derivatives (DEs) in plasma and urine samples were determined using liquid chromatography-mass spectrometry. At the initial sampling time (5 minutes), the mean (± standard deviation) peak concentration of plasma epitubatin was 879 ± 251 ng/mL, followed by a biexponential decrease in concentration, with a mean distribution half-life of 5 ± 2.5 minutes and a mean terminal elimination half-life of 1.13 ± 0.17 hours. The plasma epitubatin concentration and radioactivity levels decreased synchronously, with the majority of the radioactivity (82.4%) attributed to epitubatin. Within 72 hours of administration of ¹⁴C-epitubatin, approximately 73% of the administered radioactivity was recovered. The primary route of elimination was urine (accounting for 98% of the total recovered radioactivity), while fecal (1.5%) and respiratory (0.8%) excretions were less significant. Eptifibatide is cleared via renal and non-renal mechanisms, with renal clearance accounting for approximately 40% of total clearance. In the first 24 hours after administration, the drug is primarily excreted in the urine as unmodified Eptifibatide (34%), DE (19%), and a more polar metabolite (13%). Plasma clearance of Eptifibatide is directly proportional to body weight and estimated creatinine clearance, and inversely proportional to age. Following a single intravenous injection of (14)C radiolabeled Eptifibatide (135 μg/kg) in healthy men, renal clearance was on average approximately 40–50% of systemic clearance. Clearance was reduced by 50% in patients with moderate to severe renal impairment (estimated creatinine clearance less than 50 mL/min). Systemic clearance was lower in older patients with coronary artery disease than in younger adults. For more complete data on absorption, distribution, and excretion of Eptifibatide (9 items), please visit the HSDB records page.

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Metabolism/Metabolites
Major metabolites have not been detected in human plasma. Deamidated epitubatide and other more polar metabolites were detected in urine.
(14) C-epitubatide is extensively metabolized in rats and monkeys to deamidated epitubatide and several polar metabolites. Drug-derived radioactive material excreted in rat bile was identified as deamidated epitubatide, which was reabsorbed by the intestine and further metabolized to more polar metabolites. Plasma and urinary metabolite profiles in rats and monkeys indicate that the metabolic distribution of epitubatide is similar in both species.
Epitubatide is primarily metabolized via deamidation to a metabolite that has approximately 41% of the platelet aggregation inhibitory activity of the parent compound, and is also metabolized via the formation of other more polar metabolites. Approximately 27% of the dose of epitubatide is broken down in plasma into naturally occurring amino acids; major non-amino acid metabolites were not detected in human plasma.

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Biological half-life
Approximately 2.5 hours
In cynomolgus monkeys, a single intravenous injection of 2 mg/kg (14)C-epitibatide resulted in a decrease in plasma (14)C-epitibatide-derived radioactivity, with a half-life of approximately 12 hours. Five minutes after administration, approximately 93% of the total plasma 14C was unmetabolized and rapidly eliminated, with a half-life of 17 minutes.
In rats, a single intravenous injection of 2 mg/kg of the radiolabeled drug resulted in a rapid decrease in plasma 14C-epitibatide-derived radioactivity, with a terminal half-life of approximately 5 hours. The apparent half-life of unmetabolized epitibatide is approximately 8 minutes. Following single intravenous injections of 2 mg/kg and 20 mg/kg, plasma concentrations of epitubatide were dose-dependent, while the half-life (11 to 12 minutes) was dose-independent, indicating linear kinetics within the 2 to 20 mg/kg dose range. The mean half-life of epitubatide in patients with coronary artery disease is 2.5–2.8 hours. The mean half-life of the drug in healthy individuals has been reported to be 0.83–2.4 hours. …This study aimed to describe the distribution of (14)C-epitubatide in humans following a single intravenous (IV) bolus dose. Eight healthy men received a single intravenous bolus of 135 μg/kg of (14)C-epitubatide (approximately 50 μCi). ...At the initial sampling time (5 minutes), the mean (± standard deviation) peak plasma concentration of eptifibatide was 879 ± 251 ng/mL. Subsequently, the concentration typically decreased exponentially, with a mean distribution half-life of 5 ± 2.5 minutes and a mean terminal elimination half-life of 1.13 ± 0.17 hours. ...

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Approximately 25% of eptifibatide is protein-bound under physiological conditions, while the rest remains free and pharmacologically active in the circulation [1].
The primary route of excretion is through the renal system from the plasma compartment, with no apparent active metabolites [1].
Elimination half-life is 1-3 hours, dependent on overall renal function [1].
The pharmacokinetics of eptifibatide can be modelled by a two-compartment model with first-order elimination [1].
In the PRIDE substudy, population pharmacokinetic parameters for patients undergoing PCI: volume of distribution ranged from 0.203-0.229 L/kg; distribution half-life (t1/α) from 0.22-0.52 hours; terminal half-life (t1/β) from 2.57-2.71 hours, consistent with first-order kinetics [1].
Using a population approach with a two-compartment model, the predicted eptifibatide concentration after an initial 180 μg/kg bolus and 8 hours of 2 μg/kg/min infusion was 1619 μg/L, close to the observed mean of 1645 μg/L. This steady-state concentration is approximately the threshold (1650 μg/L) that achieves about 80% platelet GPIIb/IIIa receptor occupancy and >80% inhibition of ex vivo platelet aggregation to 20 μmol/L ADP [1].
The estimated steady-state eptifibatide concentrations from the IMPACT II regimen (135 μg/kg bolus + 0.5 or 0.75 μg/kg/min infusion) were in the 350-500 nmol/L range. Extrapolating without calcium-chelating anticoagulants, this would have inhibited ADP-induced aggregation by <30% [1].

Toxicity Summary
Identification and Use: Eptifibatide (trade name: Integrilin) is indicated for reducing the composite endpoint of death, new-onset myocardial infarction (MI), or urgent intervention requirement in patients undergoing percutaneous coronary intervention (PCI), including coronary artery stenting. Human Exposure and Toxicity: Information on acute toxicity of eptifibatide is limited. Generally, overdose of eptifibatide in humans may produce extended effects of the drug's pharmacological action, primarily manifested as bleeding. Case reports of eptifibatide-related thrombocytopenia highlight the importance of monitoring platelet counts after treatment with this drug. In a human lymphocyte chromosomal aberration assay, eptifibatide did not demonstrate genotoxicity. Animal Studies: Single-dose toxicity studies were conducted in rats, rabbits, and monkeys; at doses up to 500 μg/kg/min, administered via continuous intravenous infusion over 90 minutes, no death occurred, and all animals tolerated the drug well. In rabbits, female rabbits receiving 50 and 500 μg/kg/min (lasting 90 minutes) showed a dose-dependent decrease in platelet count, attributed to eptifibatide administration. In monkeys, the observed adverse effects were limited to petechial hemorrhage in the thigh and/or abdomen, lasting 1 to 3 days. Three out of five monkeys died or were euthanized during the study period due to anemia caused by contusions, excessive bleeding, and/or petechial hemorrhage. Total albumin and globulin levels were decreased in all monkeys. Autopsy revealed focal hemorrhage in multiple organs. In a rat fertility study, administration of eptifibatide had no effect on the pregnancy process. No fertility or parental toxicity was observed at daily doses up to 72.0 mg/kg (equivalent to 24 times the maximum recommended daily dose for humans), nor were any effects on parental reproductive function observed. In the Ames study, eptifibatide did not show genotoxicity at doses up to 667 μg/mL; in the mouse lymphoma cell forward mutation assay, eptifibatide also did not show genotoxicity at doses up to 1,000 μg/mL; and in the mouse micronucleus assay, eptifibatide did not show genotoxicity.

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Effects during pregnancy and lactation
◉ Overview of use during lactation
There is currently no publicly available information regarding the use of eptifibatide during lactation. Because eptifibatide is a peptide drug, it is unlikely to be absorbed by infants, as it is likely to be destroyed in the infant's gastrointestinal tract. Until more data are available, lactating women should use eptifibatide with caution, especially when breastfeeding newborns or premature infants. If a lactating woman uses this drug, the infant should be closely monitored for bruising and bleeding.
◉ Effects on breastfed infants
As of the revision date, no relevant published information was found.
◉ Effects on Lactation and Breast Milk
As of the revision date, no relevant published information was found.

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Protein Binding
Approximately 25%

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Interactions
Concomitant use of platelet aggregation inhibitors and anticoagulants (especially at high doses) may increase the risk of bleeding; therefore, close monitoring for bleeding is necessary, especially at arterial puncture sites. In case of severe bleeding (e.g., ineffective pressure hemostasis), epitubatide and concomitant heparin therapy should be discontinued immediately, and appropriate treatment measures should be taken as needed (e.g., protamine sulfate can be used in patients receiving heparin). In healthy individuals, enoxaparin sodium (1 mg/kg, subcutaneously every 12 hours for a total of 4 times) does not alter the pharmacokinetics or pharmacodynamics (platelet aggregation) of epitubatide. The manufacturer notes that caution should be exercised when epitubatide is used concomitantly with oral anticoagulants. In a small number of patients with acute myocardial infarction, eptifibatide has been used in combination with thrombolytic agents (e.g., alteplase, streptokinase, tenecteplase) to reduce the risk of re-occlusion of the infarct-related artery. Some clinicians believe that combining short-acting platelet aggregation inhibitors such as eptifibatide with thrombolytic therapy may achieve optimal efficacy while minimizing the risk of bleeding. However, the use of drugs affecting platelet function after thrombolysis may increase the risk of thrombolytic therapy-related bleeding complications, including complications requiring transfusions, and its efficacy has not been definitively proven to date; therefore, the combination of eptifibatide and thrombolytic therapy should be considered an investigational treatment and should be conducted with caution. Limited preclinical and clinical data indicate that in patients receiving eptifibatide (0.5 mcg/kg/min, intravenous infusion) monotherapy or in combination with aspirin, heparin, or both, there are no significant pharmacokinetic or pharmacodynamic interactions (e.g., additive effects on platelet aggregation inhibition) between eptifibatide and aspirin. While eptifibatide combined with aspirin can prolong bleeding time up to five times from baseline, a similar prolongation of bleeding time has been observed when aspirin is combined with placebo. However, because eptifibatide inhibits platelet aggregation, caution should be exercised when used in combination with other drugs that affect hemostasis, including thrombolytics, oral anticoagulants, nonsteroidal anti-inflammatory drugs (NSAIDs), or dipyridamole. In a large, multicenter clinical study (ESPRIT), eptifibatide was routinely used in combination with clopidogrel or ticlopidine in patients undergoing coronary artery stenting. To minimize potential additive pharmacological effects, the manufacturer of eptifibatide states that concomitant treatment with other platelet glycoprotein (GP IIb/IIIa) receptor inhibitors (e.g., abciximab, tirofiban) should be avoided.

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Bleeding times start to be significantly prolonged at 90% platelet inhibition [1].
In the PURSUIT trial, by 30 days there were more red-cell transfusions noted in the eptifibatide-treated group (eptifibatide 11.6%, placebo 9.2%; relative risk 1.3, 95% CI 1.1-1.4), although stroke (eptifibatide 0.7%, placebo 0.8%; p=0.41) and thrombocytopenia (eptifibatide 6.8%, placebo 6.7%) were not increased in eptifibatide-treated patients [1].
In the PRIDE substudy, despite using relatively large dosages of eptifibatide, bleeding times had returned to ≤30 minutes in all groups within 4 hours of termination of infusion [1].

[1]. Platelet glycoprotein IIb/IIIa inhibitors in percutaneous coronary intervention: focus on the pharmacokinetic-pharmacodynamic relationships of eptifibatide. Clin Pharmacokinet. 2003;42(8):703-20.

Eptifibatide is a synthetic homocyclic peptide composed of N(α)-(3-mercaptopropionyl)arginyl, glycyl, aspartic, tryptophanyl, proline, and cysteine residues linked sequentially and cyclized by disulfide bonds. Derived from a protein in the venom of the southeastern dwarf rattlesnake (Sistrurus miliarus barbouri), Eptifibatide is an anticoagulant that inhibits platelet aggregation by selectively blocking platelet glycoprotein IIb/IIIa receptors, thereby preventing the binding of fibrinogen, von Willebrand factor, and other adhesion ligands. It is used to treat unstable angina and in patients undergoing coronary angioplasty and stent implantation. It is both a platelet aggregation inhibitor and an anticoagulant. It is an organic disulfide, macrocyclic compound, and homocyclic peptide.
A synthetic cyclic hexapeptide that binds to platelet receptor glycoproteins and inhibits platelet aggregation. Eptifibatide, derived from the venom of the southeastern dwarf rattlesnake (Sistrurus miliarus barbouri), is a cyclic heptapeptide belonging to the arginine-glycine-aspartic acid analogue class of drugs. Eptifibatide is a platelet aggregation inhibitor. Its physiological action is achieved by reducing platelet aggregation. Eptifibatide is a cyclic heptapeptide with anticoagulant activity. Eptifibatide selectively and reversibly binds to and blocks platelet glycoprotein IIb/IIIa receptors. This prevents the binding of fibrinogen, von Willebrand factor, and other adhesion ligands, thereby inhibiting platelet aggregation and preventing thrombosis. This cyclic peptide, as a platelet glycoprotein IIb-IIIa antagonist, reversibly inhibits the binding of fibrinogen, von Willebrand factor, and other adhesion molecules to platelet glycoprotein IIb-IIIa receptors. It is used to treat unstable angina and in patients undergoing coronary angioplasty and stent implantation. Drug Indications For the treatment of myocardial infarction and acute coronary syndrome. FDA Label Etibatide Accord is intended for use in combination with acetylsalicylic acid and unfractionated heparin. Etibatide Accord is indicated for the prevention of early myocardial infarction in adult patients with unstable angina or non-Q-wave myocardial infarction whose last episode of chest pain occurred within 24 hours and who have ECG changes and/or elevated cardiac enzymes. Patients most likely to benefit from treatment with epitaphthide Accord are those at high risk of myocardial infarction within 3–4 days of the onset of acute angina symptoms, such as those who may require early percutaneous transluminal coronary angioplasty (PTCA). Integrilin is indicated for use in combination with acetylsalicylic acid and unfractionated heparin. Integrilin is indicated for the prevention of early myocardial infarction in patients with unstable angina or non-Q-wave myocardial infarction whose last episode of chest pain occurred within 24 hours and who have ECG changes and/or elevated cardiac enzymes. Patients most likely to benefit from integrilin treatment are those at high risk of myocardial infarction within 3-4 days of the onset of acute angina symptoms, such as those who may require early percutaneous transluminal coronary angioplasty (PTCA). Mechanism of Action Eptifibatide inhibits platelet aggregation by reversibly binding to platelet receptor glycoprotein (GP) IIb/IIIa on human platelets, thereby preventing the binding of fibrinogen, von Willebrand factor, and other adhesion ligands. Platelet aggregation inhibition is dose- and concentration-dependent. Therapeutic Uses Platelet Aggregation Inhibitors
/Clinical Trials/ ClinicalTrials.gov is a registry and results database of human clinical studies funded by public and private institutions worldwide. This website is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each record on ClinicalTrials.gov includes a summary of the study protocol, including: the disease or condition; the intervention (e.g., the medical product, behavior, or procedure being investigated); the title, description, and design of the study; participation requirements (eligibility criteria); the location of the study; contact information for the study location; and links to relevant information from other health websites, such as MedlinePlus (for patient health information) and PubMed (for citations and abstracts of academic articles in the medical field) from the NLM. Eptimethotide is included in the database. Eptimethotide is indicated for reducing the incidence of the composite endpoint of death or new myocardial infarction (MI) in patients with acute coronary syndrome (ACS) (unstable angina (UA)/non-ST-segment elevation myocardial infarction (NSTEMI)), including patients receiving medical therapy and those undergoing percutaneous coronary intervention (PCI). Eptimethotide is indicated for reducing the incidence of the composite endpoint of death, new myocardial infarction (MI), or emergency intervention in patients undergoing percutaneous coronary intervention (PCI), including those undergoing coronary artery stenting. /Included in US Product Labelling/
In a small number of patients, eptifibatide has been used in combination with thrombolytic agents (e.g., alteplase, tenecteplase) to prevent coronary re-occlusion after acute myocardial infarction. /Not Included in US Product Labelling/

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Drug Warnings
The most common and serious side effect of eptifibatide treatment is bleeding. In clinical studies, bleeding complications were reported in 35% to 75% of patients receiving different doses of eptifibatide. These complications are usually mild and occur at the vascular access site (e.g., femoral artery puncture) (e.g., patients undergoing percutaneous coronary intervention (PCI)). Bleeding is an extension of the pharmacological action of eptifibatide and is classified primarily according to the criteria of the Thrombolysis in Myocardial Infarction (TIMI) study group in clinical trials. Minor bleeding is generally defined as spontaneous gross hematuria or spontaneous hematemesis; observed blood loss with a decrease in hemoglobin concentration of 3-5 g/dL or a decrease in hematocrit of at least 10%; or a decrease in hemoglobin or hematocrit of 4-5 g/dL or 12-15%, respectively, without a clearly identifiable site of bleeding. Major bleeding is defined as intracranial hemorrhage or significant bleeding with a decrease in hemoglobin or hematocrit of at least 5 g/dL or at least 15%. Because eptifibatide increases the risk of bleeding, it is contraindicated in patients with a history of bleeding tendency or active abnormal bleeding within the past 30 days (e.g., elevated hemostatic parameters, recent non-compressive vascular puncture, gastrointestinal or genitourinary bleeding). A low baseline hematocrit (below 30%) may indicate recent undetected bleeding, and such patients may not tolerate additional bleeding events; therefore, eptifibatide should not be used in these patients. Eptifibatide is contraindicated in patients with: severe uncontrolled hypertension (systolic blood pressure ≥200 mmHg or diastolic blood pressure ≥110 mmHg, and receiving antihypertensive therapy); recent (within 6 weeks) major surgery; history of stroke or any hemorrhagic stroke within 30 days; currently receiving or planning to receive other GP IIb/IIIa receptor inhibitor therapy; and patients undergoing renal dialysis. There are currently no data on the use of Eptifibatide in patients with serum creatinine concentrations ≥ 4 mg/dL; patients with serum creatinine concentrations between 2 and 4 mg/dL should have a reduced dose.
FDA Pregnancy Risk Classification: B / No evidence of risk in humans. Although adverse reactions have been observed in animal studies, adequate, well-controlled studies in pregnant women have not shown an increased risk of fetal malformations; or, in the absence of adequate human studies, animal studies have shown no fetal risk. The possibility of fetal harm is small, but the possibility still exists. /
The safety and efficacy of integrilin in pediatric patients have not been studied. For more complete data on epitubatide (15 total), please visit the HSDB records page.

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Pharmacodynamics
Epitubatide is an anticoagulant that selectively and reversibly blocks platelet glycoprotein IIb/IIIa receptors.

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Eptifibatide is a truncated derivative of the naturally occurring rattlesnake venom protein barbourin. It is a cyclic heptapeptide that mimics the tertiary structure found in the parent compound, allowing it to bind receptors with the KGD (Lys-Gly-Asp) peptide recognition sequence [1].
Eptifibatide is a competitive antagonist for the activated platelet glycoprotein IIb/IIIa receptor. Its mechanism of action involves preventing the binding and cross-linking of fibrinogen to the platelet surface. This binding site for fibrinogen is associated with five Ca2+ ions that help maintain the tertiary structure of the receptor and affect the affinity of other ligands such as eptifibatide [1].
The binding of eptifibatide to the GPIIb/IIIa receptor involves displacement of receptor-associated Ca2+ from the activated binding site [1].
Eptifibatide is used for the treatment of acute coronary syndromes (ACS) and during percutaneous coronary interventions (PCI) to reduce thrombotic complications [1].
The FDA initially approved eptifibatide at the dosage tested in IMPACT II for the PCI indication, but subsequent pharmacokinetic and pharmacodynamic data suggested that this dose was a marked underestimate of the effective dose [1].
The ESPRIT trial demonstrated that a double-bolus regimen (two 180 μg/kg boluses 10 minutes apart + 2 μg/kg/min infusion) provides effective platelet inhibition during the critical early period of PCI when endothelial damage occurs [1].

C35H49N11O9S2

831.96

831.315

188627-80-7

Eptifibatide monoacetate;1248559-53-6

448812

White to off-white solid powder

1.6±0.1 g/cm3

1.735

-4.84

10

12

10

57

1520

5

C1C[C@H]2C(=O)N[C@@H](CSSCCC(=O)N[C@H](C(=O)NCC(=O)N[C@H](C(=O)N[C@H](C(=O)N2C1)CC3=CNC4=CC=CC=C43)CC(=O)O)CCCCN=C(N)N)C(=O)N

2-((3R,11S,17S,20S,25aS)-20-((1H-indol-3-yl)methyl)-3-carbamoyl-11-(4-guanidinobutyl)-1,9,12,15,18,21-hexaoxodocosahydro-7H-pyrrolo[2,1-g][1,2]dithia[5,8,11,14,17,20]hexaazacyclotricosin-17-yl)acetic acid

CZKPOZZJODAYPZ-LROMGURASA-N

Eptifibatide Integrilin Integrelin HSDB 8313

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~250 mg/mL (~300.50 mM)
H2O : ~50 mg/mL (~60.10 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (2.50 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (2.50 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (2.50 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 100 mg/mL (120.20 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)