title: Activity of a synthetic hexadecasaccharide (SanOrg123781A) in a pig model of arterial thrombosis.
abstract: The activity of SanOrg123781A, a new synthetic antithrombotic drug inhibiting both factor Xa and thrombin through antithrombin (AT), was compared to that of unfractionated heparin (UFH) and of the synthetic pentasaccharide (fondaparinux, SP) in an ex vivo arterial thrombosis model in the pig. Six groups of four pigs were administered intravenously with SanOrg123781A (1, 3, 10 and 30 nmol kg(-1)), UFH (30 nmol kg(-1)) or SP (30 nmol kg(-1)). In this arterial model in which platelet thrombus was formed on a thrombogenic surface under a constant high shear rate, UFH and SP had moderate antithrombotic effects while SanOrg123781A exhibited a strong, dose-dependent inhibitory activity on platelet adhesion and platelet thrombus formation. In contrast to UFH, SanOrg123781A did not modify the activated partial thromboplastin time (aPTT) even at 30 nmol kg(-1), but strongly inhibited thrombin generation. At the same dose, despite a lower antithrombotic activity than SanOrg123781A, UFH significantly affected all the coagulation parameters. Taken together, these results show that SanOrg123781A, due to its potent and selective antifactor Xa and antifactor IIa activities is a promising new antithrombotic agent even in arterial setting.
authors.affiliation: Laboratoire de Thrombose et d'Athérosclérose, IVS-INSERM Hôpital Lariboisière, Paris and INRA, Jouy en Josas, France. claire.bal@lrb.ap-hop-paris.fr
authors.forename: C
authors.initials: C
authors.lastname: Bal dit Sollier
authors.forename: C
authors.initials: C
authors.lastname: Kang
authors.forename: N
authors.initials: N
authors.lastname: Berge
authors.forename: J P
authors.initials: JP
authors.lastname: Herault
authors.forename: M
authors.initials: M
authors.lastname: Bonneau
authors.forename: J M
authors.initials: JM
authors.lastname: Herbert
authors.forename: L
authors.initials: L
authors.lastname: Drouet
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D065427:Factor Xa Inhibitors; D000077425:Fondaparinux; D006493:Heparin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D010314:Partial Thromboplastin Time; D011134:Polysaccharides / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D011516:Prothrombin / Q000037:antagonists & inhibitors; D013552:Swine; D013927:Thrombosis / Q000188:drug therapy* / Q000517:prevention & control
chemical_list: D065427:Factor Xa Inhibitors; D011134:Polysaccharides; C464792:SanOrg 123781; D011516:Prothrombin; C025337:Factor IIa; D006493:Heparin; D000077425:Fondaparinux