ABSTRACT
Pentasaccharide is the first of a new class of antithrombotic agents distinct from low-molecular-
weight heparins and heparin. It is a totally synthetic agent that exhibits only factor (F) Xa
inhibitor activity. It is dependent on binding to antithrombin III (AT) for eliciting its
antithrombotic action. It has an anti-FXa activity of about 700U=mg. The aPTT is minimally affected by pentasaccharide. It has dose-dependent antithrombotic activity in several animal
models of thrombosis. The antithrombotic activity is related to the inhibition of thrombin
generation through anti-FXa activity, although the maximal inhibition of thrombin generation
was less than that for heparin. Plasma AT saturation occurs at high dosages and loss of anti-FXa
activity occurs at AT levels of 50% or less. It does not release TFPI. No platelet interactions have
been observed, even in systems positive to heparin-induced thrombocytopenia. There is no
platelet factor 4 (PF4) interaction with pentasaccharide. Protamine sulfate does not neutralize the
actions of pentasaccharide; however, heparinase I and heparinase II do cleave and inactivate
pentasaccharide. Pharmacokinetic studies reveal nearly complete subcutaneous bioavailability,
rapid onset of action, a prolonged half-life in both intravenous ( 4 h) and subcutaneous dosing ( 15 h) regimens and no metabolism with renal excretion. Animal studies suggest only minor bleeding at dosages far higher than required for complete protection against induced thrombosis.
Phase II clinical studies have identified a dose of 2.5mg once daily for prophylaxis of venous
thrombosis. Four phase III studies (n> 8000) have demonstrated a 50% relative risk reduction of venous thromboembolic events in orthopedic surgery patients in comparison to low-molecular-
weight heparin. The bleeding, as a measure of safety, however, was significantly higher
statistically, in comparison with low-molecular-weight heparin. Clinical trials of pentasaccharide
