Pharmacodynamics and pharmacokinetics of eptifibatide in patients with acute coronary syndromes - Prospective analysis from PURSUIT

Background-Platelet deposition and aggregation are central to the pathogene sis of ischemic complications of acute coronary syndromes (ACS). Pharmacody namic 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 patient s enrolled in the Platelet glycoprotein IIb/IIIa in Unstable angina: Recept or Suppression Using Integrilin (eptifibatide) Therapy (PURSUIT) trial of A CS. Methods and Results-Patients were randomly assigned to an intravenous bolus (180 mug/kg) and 72-hour infusion of eptifibatide (2.0 mug/kg per minute, n=48) or placebo (n=50). We assessed correlations of plasma eptifibatide le vels with receptor occupancy and inhibition of ex. vivo platelet aggregatio n 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 citrat e 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 r eceptor agonist peptide versus ADP stimulation; inhibition of platelet aggr egation was greater in blood samples anticoagulated with citrate versus D-p henylalanyl-L-prolyl-L-arginine chloromethylketone (PPACK). Plasma eptifiba tide levels correlated significantly with receptor occupancy but not with i nhibition of platelet aggregation. Conclusions-A bolus and infusion of eptifibatide inhibits platelet aggregat ion profoundly in patients with ACS and is followed by brief, partial recov ery. These results enhance our understanding of the relation between pharma codynamic and clinical effects of eptifibatide in such patients and may hav e important implications for its use in percutaneous interventions.