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(Circulation. 2001;104:399.)
© 2001 American Heart Association, Inc.

Clinical Investigation and Reports

Pharmacodynamics and Pharmacokinetics of Eptifibatide in Patients With Acute Coronary Syndromes

Prospective Analysis From PURSUIT

Barbara E. Tardiff, MD; Lisa K. Jennings, PhD; Robert A. Harrington, MD; Daniel Gretler, MD; Richard F. Potthoff, PhD; David A. Vorchheimer, MD; Paul R. Eisenberg, MD; A. Michael Lincoff, MD; Marino Labinaz, MD; Diane M. Joseph, BS; Mark F. McDougal, BA; Neal S. Kleiman, MD; , for the PERIGEE Investigators

From Duke Clinical Research Institute, Durham, NC (B.E.T., R.A.H., R.F.P., D.M.J., M.F.M); the University of Tennessee, Memphis (L.K.J.); COR Therapeutics, Inc, South San Francisco, Calif (D.G); Mt Sinai Medical Center, New York, NY (D.A.V.); Washington University, St Louis, Mo (P.R.E); the Cleveland Clinic Foundation, Cleveland, Ohio (A.M.L.); the University of Ottawa Heart Institute, Ottawa, Ontario, Canada (M.L.); and Baylor College of Medicine, Methodist DeBakey Heart Center Hospital, Houston, Tex (N.S.K.).

Correspondence to Neal S. Kleiman, MD, Methodist Hospital, 6565 Fannin, MS F1090, Houston, TX 77030. E-mail nkleiman{at}bcm.tmc.edu

Background— Platelet deposition and aggregation are central to the pathogenesis of ischemic complications of acute coronary syndromes (ACS). Pharmacodynamic effects of the platelet glycoprotein IIb/IIIa antagonist eptifibatide have been delineated in healthy subjects but not in patients with ACS. We assessed effects of eptifibatide on ex vivo platelet aggregation in patients enrolled in the Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin (eptifibatide) Therapy (PURSUIT) trial of ACS.

Methods and Results— Patients were randomly assigned to an intravenous bolus (180 µg/kg) and 72-hour infusion of eptifibatide (2.0 µg/kg per minute, n=48) or placebo (n=50). We assessed correlations of plasma eptifibatide levels with receptor occupancy and inhibition of ex vivo platelet aggregation at 5 minutes and 1, 4, 24, 48, and 72 hours during treatment and 4 and 8 hours after termination of infusion. Blood was collected in buffered citrate and D-phenylalanyl-L-prolyl-L-arginine chloromethylketone anticoagulants. Although eptifibatide produced profound, prolonged inhibition of platelet aggregation during therapy, aggregation appeared to recover partially by 4 hours after the bolus. The aggregation response was greater with thrombin receptor agonist peptide versus ADP stimulation; inhibition of platelet aggregation was greater in blood samples anticoagulated with citrate versus D-phenylalanyl-L-prolyl-L-arginine chloromethylketone (PPACK). Plasma eptifibatide levels correlated significantly with receptor occupancy but not with inhibition of platelet aggregation.

Conclusions— A bolus and infusion of eptifibatide inhibits platelet aggregation profoundly in patients with ACS and is followed by brief, partial recovery. These results enhance our understanding of the relation between pharmacodynamic and clinical effects of eptifibatide in such patients and may have important implications for its use in percutaneous interventions.

Key Words: pharmacokinetics • platelets • coronary disease • glycoproteins

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