Eptifibatide | Encyclopeptide

Chemical Identity

Property	Value
Chemical Formula	C35H49N11O9S2
Molecular Weight	831.96 g/mol
CAS Number	188627-80-7
IUPAC Name	Cyclic heptapeptide disintegrin analog
Peptide Class	GPIIb/IIIa Inhibitor
Origin	Synthetic (inspired by barbourin)

Structure

Eptifibatide is a synthetic cyclic heptapeptide containing six amino acids plus a mercaptopropionyl (des-amino cysteinyl) residue. It is modeled after the Lys-Gly-Asp (KGD) sequence found in barbourin, a disintegrin from the venom of the southeastern pygmy rattlesnake (Sistrurus miliarius barbourin). The disulfide bridge between the N-terminal cysteine and the penultimate cysteine creates a conformationally constrained ring that mimics the RGD integrin recognition motif.

Mechanism of Action

Eptifibatide reversibly binds to the glycoprotein IIb/IIIa (GPIIb/IIIa) integrin receptor on activated platelets, blocking the binding of fibrinogen and von Willebrand factor. This prevents the final common pathway of platelet aggregation, regardless of the activating stimulus. The KGD sequence confers selectivity for GPIIb/IIIa over other integrins.

Clinical Applications

Eptifibatide (Integrilin) is approved for:

Acute coronary syndromes (ACS): Unstable angina and non-ST-elevation MI, with or without early invasive strategy
Percutaneous coronary intervention (PCI): Adjunctive antiplatelet therapy during coronary stenting

Administered as a 180 mcg/kg IV bolus followed by 2 mcg/kg/min infusion for up to 72-96 hours (ACS) or 18-24 hours post-PCI.

Pharmacokinetics

Half-life: 2.5 hours
Tmax: Immediate (IV bolus)
Protein binding: 25%
Metabolism: Minimal; primarily renal elimination
Onset of action: >80% platelet inhibition within 15 minutes of bolus

Safety and Side Effects

Bleeding (dose-limiting, major bleeding 1-10%), thrombocytopenia (<1%), and hypotension. Contraindicated in patients with active bleeding, recent surgery, severe hypertension, or thrombocytopenia (<100,000/mcL). Platelet counts should be monitored. Bleeding risk is reduced compared to abciximab due to reversible binding and short half-life.

References

The PURSUIT Trial Investigators. (1998). Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes. New England Journal of Medicine, 339, 436-443.
Tcheng, J.E., et al. (2001). Enhanced efficacy of eptifibatide by early administration in patients undergoing coronary intervention. American Journal of Cardiology, 88, 722-727.