PMID- 14667957
OWN - NLM
STAT- MEDLINE
DCOM- 20040120
LR  - 20190922
IS  - 0149-2918 (Print)
IS  - 0149-2918 (Linking)
VI  - 25
IP  - 10
DP  - 2003 Oct
TI  - Pharmacokinetic and pharmacodynamic properties of eptifabatide in healthy 
      subjects receiving unfractionated heparin or the low-molecular-weight heparin 
      enoxaparin.
PG  - 2564-74
AB  - BACKGROUND: The rationale for the combined use of glycoprotein (GP) IIb/Illa 
      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 (180 microg/kg bolus + 2.0 
      microg/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 (Css); 
      secondary end points included the inhibition of platelet aggregation, area under 
      the plasma-concentration time curve, apparent volume of distribution, plasma 
      elimination half-life (t 1/2), and total body eptifibatide clearance (Cl). 
      RESULTS: A total of 14 subjects (10 men, 4 women; mean [SD] age, 53.2 [6.0]years) 
      were enrolled. The mean (SD) Css of eptifibatide was essentially identical when 
      it was coadministered with either UFH or enoxaparin (1640 [227] ng/mL and 1610 
      (229) ng/mL, respectively). In addition, no clinically significant differences 
      were found between the coadministration of UFH versus enoxaparin in platelet 
      aggregation inhibition, t 1/2, eptifibatide Cl, or other pharmacokinetic 
      parameters. Both regimens were well tolerated; no serious adverse effects were 
      reported. CONCLUSION: The results in this population of healthy subjects, 
      age-matched to the intended target population, suggest that eptifibatide can be 
      used in the treatment of NSTE ACS effectively, with good tolerability, and 
      without dose adjustment when coadministered with enoxaparin instead of with UFH.
FAU - Gretler, Daniel D
AU  - Gretler DD
AD  - Millennium Pharmaceuticals, Inc., 256 East Grand Avenue, South San Francisco, CA 
      94080, USA. dan.gretler@mpi.com
LA  - eng
PT  - Clinical Trial
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 0 (Peptides)
RN  - 0 (Platelet Aggregation Inhibitors)
RN  - 9005-49-6 (Heparin)
RN  - EC 3.4.21.5 (Thrombin)
RN  - NA8320J834 (Eptifibatide)
SB  - IM
MH  - Aged
MH  - Area Under Curve
MH  - Chromatography, Liquid
MH  - Cross-Over Studies
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions
MH  - Eptifibatide
MH  - Female
MH  - Half-Life
MH  - Heparin/*pharmacology
MH  - Heparin, Low-Molecular-Weight/pharmacology
MH  - Humans
MH  - Injections, Intravenous
MH  - Male
MH  - Mass Spectrometry
MH  - Middle Aged
MH  - Peptides/*pharmacokinetics/pharmacology
MH  - Platelet Aggregation Inhibitors/*pharmacokinetics/pharmacology
MH  - Thrombin/*antagonists & inhibitors
MH  - Time Factors
EDAT- 2003/12/12 05:00
MHDA- 2004/01/21 05:00
CRDT- 2003/12/12 05:00
PHST- 2003/12/12 05:00 [pubmed]
PHST- 2004/01/21 05:00 [medline]
PHST- 2003/12/12 05:00 [entrez]
AID - S014929180380317X [pii]
AID - 10.1016/s0149-2918(03)80317-x [doi]
PST - ppublish
SO  - Clin Ther. 2003 Oct;25(10):2564-74. doi: 10.1016/s0149-2918(03)80317-x.