Abstract
Because of the unsatisfactory options available for safe and effective antithrombotic
therapy, recent, intense research and development efforts have focused on direct,
or site-directed, thrombin inhibitors. Argatroban is a small-molecule, reversible,
direct thrombin inhibitor selective for the catalytic site of the thrombin molecule.
Argatroban's molecular properties (small molecule; fast, selective, and reversible
inhibition of the thrombin catalytic site; and similar in vitro potency for inhibiting
both clotbound and soluble thrombin) offer the potential for significant antithrombotic
efficacy with minimal systemic anticoagulant effects. Its clinical pharmacologic properties
offer the potential for minimal risk of bleeding, very rapid achievement of therapeutic
antithrombotic efficacy, predictable dose response, and rapid restoration of the hemostatic
systems to baseline on termination of intravenous infusion. The intravenous agent
Novastan® (brand of argatroban) is currently approved for clinical use in Japan for the treatment
of peripheral arterial occlusive disease. Novastan is in advanced clinical development
in North and South America for several indications, including (1) anticoagulant/antithrombotic
therapy in heparin-induced thrombocytopenia (HIT) and heparin-induced thrombocytopenia,
and thrombosis syndrome (HITTS); and (2) adjunctive therapy to thrombolytic agents
in acute myocardial infarction. Results from these trials are projected to be available
by early 1997.
Keywords:
Argatroban - thrombin inhibitors - anticoagulation - antithrombotic agents - thrombolysis
- pharmacology.
