title: Characterization of the antithrombotic fingerprint of the branded and copies of the low-molecular-weight enoxaparin using thrombin generation assay.
abstract: BACKGROUND
  The patent protection of low-molecular-weight heparins (LMWHs) expired, so the definition of criteria for the biological similarity between LMWH copies and the original product is a real need.
  
  
  OBJECTIVE
  The present in vitro study compared copies and branded enoxaparin using the specific anti-Xa activity and the calibrated automated thrombogram assay.
  
  
  METHODS
  Samples of platelet-poor plasma (PPP) and platelet-rich plasma (PRP) from 15 healthy volunteers were spiked with branded enoxaparin (Lovenox) or its copies (Cutenox, Dilutol, Enoxa, Fibrinox, Loparin, Lupenox, Novex, Noxprin, and Versa). The specific anti-Xa activity was measured in PPP, and thrombin generation was assessed in PPP and PRP in the presence of tissue factor or pancreatic cancer cells BXPC3.
  
  
  RESULTS
  The anti-Xa activity of enoxaparin copies ranged from 0.072 to 0.088 IU/μg, being lower as compared to the branded enoxaparin (0.095 anti-Xa IU/μg). The potency of each copy to inhibit thrombin generation varied in the 3 experimental systems. The presence of platelets or pancreatic cancer cells BXPC3 in human plasma induced significant modifications in the inhibitory efficiency of enoxaparin copies on thrombin generation, which distinguished them from the branded product.
  
  
  CONCLUSIONS
  Enoxaparin copies showed significant variability regarding their inhibitory potency on thrombin generation. Platelets and cancer cells significantly increased the variability of the antithrombotic efficiency of the copies as compared to the branded enoxaparin. The present study underlines the need for the elaboration of additional functional criteria to evaluate the global antithrombotic capacity of enoxaparin copies in order to evaluate their potential sameness with the branded drug.
authors.affiliation: Service d'Hématologie Biologique Hôpital Tenon, Hôpitaux Universitaires Est Parisien, Assistance Publique Hôpitaux de Paris, France INSERM U938, Faculté de Médecine Pierre et Marie Curie, Université Paris VI, France grigorios.gerotziafas@tnn.aphp.fr.
authors.forename: Grigoris T
authors.initials: GT
authors.lastname: Gerotziafas
authors.affiliation: INSERM U938, Faculté de Médecine Pierre et Marie Curie, Université Paris VI, France.
authors.forename: Aurèlie
authors.initials: A
authors.lastname: Rouseau
authors.affiliation: INSERM U938, Faculté de Médecine Pierre et Marie Curie, Université Paris VI, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mbemba
authors.affiliation: Service d'Hématologie Biologique Hôpital Tenon, Hôpitaux Universitaires Est Parisien, Assistance Publique Hôpitaux de Paris, France.
authors.forename: Amir
authors.initials: A
authors.lastname: Khartechi
authors.affiliation: Research and Development, Diagnostica Stago, Gennevilliers, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Van Dreden
authors.affiliation: Cardiovascular Institute Loyola University Chicago, Maywood, IL, USA.
authors.forename: Janine
authors.initials: J
authors.lastname: Walenga
authors.affiliation: Department of Pathology, Loyola University Chicago, Maywood, IL, USA.
authors.forename: Jawed
authors.initials: J
authors.lastname: Fareed
authors.affiliation: Service d'Hématologie Biologique Hôpital Tenon, Hôpitaux Universitaires Est Parisien, Assistance Publique Hôpitaux de Paris, France INSERM U938, Faculté de Médecine Pierre et Marie Curie, Université Paris VI, France.
authors.forename: Ismail
authors.initials: I
authors.lastname: Elalamy
mesh_terms: D045744:Cell Line, Tumor; D016568:Drugs, Generic / Q000493:pharmacokinetics / Q000494:pharmacology*; D017984:Enoxaparin / Q000493:pharmacokinetics / Q000494:pharmacology*; D005343:Fibrinolytic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D013917:Thrombin / Q000378:metabolism*
chemical_list: D016568:Drugs, Generic; D017984:Enoxaparin; D005343:Fibrinolytic Agents; D013917:Thrombin
keywords: LMWH; anti-Xa activity; biosimilars; enoxaparin; thrombin generation