PMID- 24237610
OWN - NLM
STAT- MEDLINE
DCOM- 20140916
LR  - 20230829
IS  - 1538-7836 (Electronic)
IS  - 1538-7836 (Linking)
VI  - 12
IP  - 1
DP  - 2014 Jan
TI  - EP42675, a synthetic parenteral dual-action anticoagulant: pharmacokinetics, 
      pharmacodynamics, and absence of interactions with antiplatelet drugs.
PG  - 24-33
LID - 10.1111/jth.12453 [doi]
AB  - BACKGROUND: EP42675 is a first-in-class, synthetic, parenteral, anticoagulant 
      combining in a single molecule a direct thrombin inhibitor and an indirect factor 
      Xa(FXa) inhibitor. OBJECTIVES: To investigate the safety, pharmacokinetics, and 
      pharmacodynamics of EP42675 and its interaction with aspirin, clopidogrel, and 
      unfractionated heparin (UFH). SUBJECTS AND METHODS: In study 1, healthy male 
      subjects were administered intravenously single-ascending doses (1-10 mg) of 
      EP42675 or placebo. In study 2, healthy male subjects were administered 
      intravenously a single dose of 5 mg EP42675 on day 1 followed by oral 
      administration of aspirin (100 mg) and clopidogrel (75 mg) once daily from day 8 
      to 21. On day 15, a second dose of 5 mg EP42675 was administered, and subjects 
      were then randomized to receive a single dose of UFH (30 or 60 IU kg(-1) ) or 
      placebo. RESULTS AND CONCLUSIONS: Mild bleedings were the only drug-related 
      adverse events. EP42675 pharmacokinetics were dose-proportional and characterized 
      by a low clearance, a small volume of distribution, a long terminal half-life. 
      EP42675 pharmacodynamics were characterized by a long-lasting, dose-dependent 
      increase in activated clotting time, ecarin clotting time, thrombin time, 
      anti-FXa activity, activated partial thromboplastin time, prothrombin time, and a 
      decrease in endogenous thrombin potential, measured by a thrombin generation 
      test. Dose-dependent additive effects were seen with UFH on coagulation tests. 
      EP42675 had no additive effect on the inhibition of platelet aggregation induced 
      by aspirin and clopidogrel. These results warrant further clinical development of 
      this new class of anticoagulant.
CI  - (c) 2013 International Society on Thrombosis and Haemostasis.
FAU - Gueret, P
AU  - Gueret P
AD  - University Hospital Pontchaillou, Rennes, France; GETBO EA 3878, Brest, France.
FAU - Krezel, C
AU  - Krezel C
FAU - Fuseau, E
AU  - Fuseau E
FAU - van Giersbergen, P L M
AU  - van Giersbergen PL
FAU - Petitou, M
AU  - Petitou M
FAU - Neuhart, E
AU  - Neuhart E
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - England
TA  - J Thromb Haemost
JT  - Journal of thrombosis and haemostasis : JTH
JID - 101170508
RN  - 0 (Anticoagulants)
RN  - 0 (EP 42675)
RN  - 0 (Oligosaccharides)
RN  - 0 (Placebos)
RN  - 0 (Platelet Aggregation Inhibitors)
SB  - IM
MH  - Anticoagulants/pharmacokinetics/pharmacology/*therapeutic use
MH  - Double-Blind Method
MH  - Drug Interactions
MH  - Half-Life
MH  - Humans
MH  - Male
MH  - Oligosaccharides/pharmacokinetics/pharmacology/*therapeutic use
MH  - Placebos
MH  - Platelet Aggregation Inhibitors/pharmacology/*therapeutic use
OTO - NOTNLM
OT  - anticoagulants
OT  - antithrombins
OT  - factor Xa
OT  - pharmacokinetics
OT  - phase 1 clinical trials
EDAT- 2013/11/19 06:00
MHDA- 2014/09/17 06:00
CRDT- 2013/11/19 06:00
PHST- 2012/09/09 00:00 [received]
PHST- 2013/11/19 06:00 [entrez]
PHST- 2013/11/19 06:00 [pubmed]
PHST- 2014/09/17 06:00 [medline]
AID - S1538-7836(22)04159-9 [pii]
AID - 10.1111/jth.12453 [doi]
PST - ppublish
SO  - J Thromb Haemost. 2014 Jan;12(1):24-33. doi: 10.1111/jth.12453.