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  • Title: Argatroban: a direct thrombin inhibitor with reliable and predictable anticoagulant actions.
    Author: Escolar G, Bozzo J, Maragall S.
    Journal: Drugs Today (Barc); 2006 Apr; 42(4):223-36. PubMed ID: 16703119.
    Abstract:
    Pharmacological strategies aimed at the prevention of thrombotic complications are in continuous development. Argatroban is a synthetic small molecule derived from l-arginine with specific antithrombotic activity. Argatroban is a direct thrombin inhibitor that binds avidly and reversibly to the catalytic site of thrombin and that does not require other cofactors to exert its antithrombotic action. Due to its selective inhibitory mechanism, argatroban blocks both circulating and clot-bound thrombin. A rapid onset of its anticoagulant action is achieved after intravenous administration. The short elimination half-life of argatroban (52+/-16 minutes) ensures a rapid restoration of hemostasis upon cessation of treatment. Argatroban produces a predictable dose response, and its anticoagulant actions can be monitored easily through the routine coagulation tests activated partial thromboplastin time (aPTT) and activated clotting time (ACT). The specific mechanism of action and favorable pharmacokinetic profile of argatroban suggest that it could be beneficial in all indications where other intravenous anticoagulants are used. Results from clinical studies performed to date show that, when administered to patients with heparin-induced thrombocytopenia (HIT) or HIT with thrombosis (HITTS) in two large-scale, nonrandomized, prospective trials, argatroban reduced a combined endpoint of morbidity and mortality when compared with historical controls. Argatroban was well tolerated in clinical trials of patients with HIT and caused no increase in bleeding risk compared with historical controls. Argatroban does not induce the formation of antibodies that can neutralize its anticoagulant effect, prolong its half-life or enhance its activity. The U.S. Food and Drug Administration has approved the use of this drug as an alternative antithrombotic treatment for patients with HIT as well as for patients with or at risk for HIT undergoing percutaneous coronary interventions. In 2004 (Sweden), 2005 (Germany, the Netherlands, Austria and Iceland) and 2006 (Denmark) argatroban was approved for anticoagulation in adult patients with heparin-induced thrombocytopenia type II who require parenteral antithrombotic therapy.
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