;
*
135-mcg/kg bolus followed by a continuous infusion of 0.5 mcg/kg/min.
†
180-mcg/kg bolus followed by a continuous infusion of 2.0 mcg/kg/min.
Inhibition of platelet aggregation 15 min after bolus 69% 84%
Inhibition of platelet aggregation at steady state 40–50% >90%
Bleeding-time prolongation at steady state <5× <5×
Inhibition of platelet aggregation 4h after infusion discontinuation <30% <50%
Bleeding-time prolongation 6h after infusion discontinuation 1× 1.4×
The eptifibatide dosing regimen used in the ESPRIT study included two 180-mcg/kg bolus doses given 10 minutes apart combined with a continuous 2.0-mcg/kg/min infusion.
When administered alone, eptifibatide has no measurable effect on prothrombin time (PT) or activated partial thromboplastin time (aPTT) (see also PRECAUTIONS, Drug Interactions section).
There were no important differences between men and women or between age groups in the pharmacodynamic properties of eptifibatide. Differences among ethnic groups have not been assessed.
Pharmacokinetics
The pharmacokinetics of eptifibatide are linear and dose-proportional for bolus doses ranging from 90 to 250 mcg/kg and infusion rates from 0.5 to 3.0 mcg/kg/min. Plasma elimination half-life is approximately 2.5 hours. Administration of a single 180-mcg/kg bolus combined with an infusion produces an early peak level, followed by a small decline prior to attaining steady state (within 4–6 hours). This decline can be prevented by administering a second 180-mcg/kg bolus 10 minutes after the first. The extent of eptifibatide binding to human plasma protein is about 25%. Clearance in patients with coronary artery disease is about 55 mL/kg/h. In healthy subjects, renal clearance accounts for approximately 50% of total body clearance, with the majority of the drug excreted in the urine as eptifibatide, deaminated eptifibatide, and other, more polar metabolites. No major metabolites have been detected in human plasma.
In patients with moderate to severe renal insufficiency (creatinine clearance <50 mL/min using the Cockcroft-Gault equation), the clearance of eptifibatide is reduced by approximately 50% and steady-state plasma levels approximately doubled (see WARNINGS and DOSAGE AND ADMINISTRATION).
Special Populations
Patients in clinical studies were older (range: 20–94 years) than those in the clinical pharmacology studies. Elderly patients with coronary artery disease demonstrated higher plasma levels and lower total body clearance of eptifibatide when given the same dose as younger patients. Limited data are available on lighter weight (<50 kg) patients over 75 years of age.
No studies have been conducted in patients with hepatic impairment.
Males and females have not demonstrated any clinically significant differences in the pharmacokinetics of eptifibatide.
CLINICAL STUDIES
Eptifibatide was studied in 3 placebo-controlled, randomized studies. PURSUIT eva luated patients with acute coronary syndromes: unstable angina (UA) or non-ST-segment elevation MI (NSTEMI). Two other studies, ESPRIT and IMPACT II, eva luated patients about to undergo a percutaneous coronary intervention (PCI). Patients underwent primarily balloon angioplasty in IMPACT II and intracoronary stent placement, with or without angioplasty, in ESPRIT.
Non-ST-segment Elevation Acute Coronary Syndrome
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