Short- and long-acting synthetic pentasaccharides as antithrombotic agents.
Fondaparinux sodium (Arixtra; GlaxoSmithKline) is the first of a new class of antithrombotic agents. It is a chemically synthesised pentasaccharide mimicking the site of heparin that binds to antithrombin. It is purely a factor Xa inhibitor and an inhibitor of thrombin generation that requires binding to antithrombin. Fondaparinux sodium differs from heparin, low-molecular-weight heparin and heparinoids, and cannot be used interchangeably. It has been approved in the US and Europe for the prophylaxis of venous thrombosis after orthopaedic surgery by a fixed dose of 2.5 mg/day without monitoring. Using this pentasaccharide as a backbone, other structures have been synthesised. Idraparinux sodium (Sanofi-Aventis) differs structurally from fondaparinux sodium as it has additional methyl groups, a long half-life, and once-weekly administration. Both drugs are being developed as antithrombotics for venous and arterial thrombosis, acute coronary syndrome, stroke and as adjuncts to thrombolytic therapy.
Walenga
Jeanine M
JM
Cardiovascular Institute (110/5226), Loyola University Medical Center, 2160 S. First Avenue, Maywood, IL 60153, USA. jwaleng@lumc.edu
Jeske
Walter P
WP
Fareed
Jawed
J
D000818:Animals; D000990:Antithrombin III / Q000008:administration & dosage / Q000737:chemistry; D003692:Delayed-Action Preparations; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000737:chemistry; D000077425:Fondaparinux; D006801:Humans; D011134:Polysaccharides / Q000008:administration & dosage* / Q000737:chemistry; D013923:Thromboembolism / Q000097:blood / Q000188:drug therapy*
D003692:Delayed-Action Preparations; D005343:Fibrinolytic Agents; D011134:Polysaccharides; D000990:Antithrombin III; D000077425:Fondaparinux