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(Chest. 2003;124:364S-370S.)
© 2003 American College of Chest Physicians

New Pentasaccharides for Prophylaxis of Deep Vein Thrombosis*

Pharmacology

Kenneth A. Bauer, MD

* From the Department of Medicine, Harvard Medical School, Hematology Section, VA Boston Healthcare System, and Beth Israel Deaconess Medical Center, Boston, MA.

Correspondence to: Kenneth A. Bauer, MD, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215; e-mail: kbauer{at}bidmc.harvard.edu

Fondaparinux is the first of a new class of antithrombotic compounds, the synthetic pentasaccharides. By binding rapidly and strongly to antithrombin, its sole physiologic target in plasma, fondaparinux catalyzes specifically the inhibition of factor Xa, which results in effective and linear dose-dependent inhibition of thrombin generation. Fondaparinux does not bind to platelets. Its antithrombotic effect has been demonstrated in several animal models of arterial and venous thrombosis. At equivalent antithrombotic concentrations, fondaparinux induced less bleeding than unfractionated heparin in experimental bleeding models. Furthermore, it did not cross-react with sera from patients with heparin-induced thrombocytopenia. Administered subcutaneously, the absorption of fondaparinux is complete, rapid, and independent of dose. It has a linear pharmacokinetic profile, and its half-life of approximately 17 h allows for once-daily dosing. Fondaparinux is almost completely excreted by the kidneys. Owing to the limited intrasubject and intersubject variability, routine monitoring and dose adjustments should not be required for most patients. Fondaparinux has been approved for use in thromboprophylaxis after major orthopedic surgery, where it has demonstrated its efficacy compared to a low-molecular-weight heparin. Its clinical development in other indications is ongoing.

Key Words: fondaparinux • idraparinux • low-molecular-weight heparin • pentasaccharide • pharmacokinetics • thromboprophylaxis • venous thromboembolism




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