Pharmacokinetic and pharmacodynamic properties of eptifabatide in healthy subjects receiving unfractionated heparin or the low-molecular-weight heparin enoxaparin

• Published in: Clinical therapeutics Vol. 25; no. 10; pp. 2564 - 2574
• Main Author: Gretler, Daniel D.
• Format: Journal Article
• Language: English
• Published: United States EM Inc USA 01.10.2003; Elsevier Limited
• Subjects: Aged; Area Under Curve; Chromatography, Liquid; Cross-Over Studies; Dose-Response Relationship, Drug; Drug Interactions; Female; Half-Life; Heparin - pharmacology; Heparin, Low-Molecular-Weight - pharmacology; Humans; Injections, Intravenous; Male; Mass Spectrometry; Middle Aged; Peptides - pharmacokinetics; Peptides - pharmacology; Platelet Aggregation Inhibitors - pharmacokinetics; Platelet Aggregation Inhibitors - pharmacology; Thrombin - antagonists & inhibitors; Time Factors
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/S0149-2918(03)80317-X

Background: The rationale for the combined use of glycoprotein (GP) IIb/IIIa inhibitors, such as eptifibatide, and antithrombin agents, such as unfractionated heparin (UFH), in patients presenting with non—ST-segment elevation (NSTE) acute coronary syndrome (ACS) and those scheduled for percutaneous coronary intervention is based on the fact that these therapies target the complementary pathophysiologic mechanisms responsible for ischemic adverse effects. The results of a recent study indicated that the combination of eptifibatide and enoxaparin is associated with a reduced rate of ischemic adverse effects compared with the combination of eptifibatide and UFH. Therefore, the coadministration of eptifibatide with enoxaparin is an attractive option for the management of patients with NSTE ACS. Objective: This study was designed to determine whether the substitution of enoxaparin for UFH, when coadministered with eptifibatide, affects the pharmacokinetic and pharmacodynamic properties of eptifibatide. Methods: This open-label, crossover study was conducted at the Quintiles Clinical Pharmacology Unit (Lenexa, Kansas). Healthy subjects were sequentially treated with the GP IIb-IIIa inhibitor eptifibatide (180μg/kg bolus + 2.0 μg/kg · min infusion) plus UFH or eptifibatide plus the low-molecular-weight heparin enoxaparin, on 2 occasions, separated by a 6- to 14-day washout period. The order of administration of the 2 regimens was random. The primary end point of the study was the steady-state plasma concentration of eptifibatide (C ss); secondary end