Introduction
Eptifibatide acetate is a white or white-off powder, soluble in water and freely soluble in 1% acetic in water, with the empirical formula C35H49N11O9S2 and molecular weight of 831.96. It is a cyclic heptapeptide which can block the platelet receptor GP IIb/IIIa and prevent the formation of platelet thrombi. It is mainly used to treat acutecoronary syndrome including unstable angina, non-Q wave myocardial infarct and patients undergoing primary percutaneous coronary intervention.
Pharmacologic action
There are no long-term animal studies that have been conducted to testify whether or not the eptifibatide has carcinogenic potential, but it has no genotoxicity and this result is supported by Ames test, positive mutation test of mouse lymphoma cells (L 5178Y, TK+/-), chromosome aberration test of human lymphocytes and micronucleus test of mice. The daily dose of continuous intravenous infusion of eptifibatide was 72 mg/kg/day, which was 4 times of the recommended daily maximum dose in terms of body surface area, and had no negative effect on fertility and reproductive ability of male and female rats.
Function
Etibapeptide is a cyclic heptapeptide that inhibits platelet aggregation by blocking the binding of fibrinogen, angiophilic factor and other adherent ligands to GPIIb/IIIa. When given intravenously, etibapeptide inhibits the aggregation of isolated platelet in a dose- and concentration-dependent manner. The inhibition of platelet aggregation is reversible after halting intravenous infusion of etibapeptide, which is believed to be due to the dissociation of etibapeptide from platelets. The platelet membrane GPIIb/IIIa receptor changed its configuration and combined with one end of fibrinogen dimer to complete platelet aggregation when the platelet was activated. So GPIIb/IIIa receptor is considered to be the last common pathway of platelet aggregation.
Pharmacokinetics and metabolism
The plasma concentration reached the peak after intravenous injection of eptifibatide 5 minutes later. The platelet function has been inhibited significantly 1 h after intravenous administration and the effect lasted for 2~4 hrs. The area under the curve was 1.06 μg. h/ml with the distribution volume 185ml/kg and the distribution half-life is 5 min. The binding rate of eptifibatide with protein was 25% and its metabolites deamination-eptifibatide and polar metabolites were not active. The primary clearance way of eptifibatide is via the kidney. The renal clearance rate of eptifibatide is 3.79 L/h, and the total clearance rate is 55~58 L/ (kg h), which occupies 71.4% of the total metabolism. Other metabolic pathways, such as respiratory pathways and fecal excretion, are nearly 1% and 1.5%, respectively. What's more, the elimination half-life of eptifibatide is 1.13 to 2.5 h, and it also can be cleared by hemodialysis.
References:
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