Argatroban: A direct thrombin inhibitor with reliable and predictable anticoagulant actions

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.

Anti-Helicobacter pyloriand Thrombin Inhibitory Components from Chinese Dragon’s Blood,Dracaena cochinchinensis

“…Positive control was provided by argatroban, which is well described in the thrombin literature. 50 DPP-IV Assay. Recombinant human DPP-IV activity was assayed in 100 mM Hepes, pH 7.5, with 0.01 nM DPP-IV, 10 µM Ala-Pro-AMC, and 2% DMSO in black 96-well plates.…”

Treatment for Patients with Acute Ischemic Stroke Presenting beyond Six Hours of Ischemic Symptom Onset : Effectiveness of Intravenous Direct Thrombin Inhibitor, Argatroban

“…This drug reversibly bind the catalytic site of thrombin and does not require other cofactors, and its anticoagulation effect is achieved after IV administration. Argatroban has the potential to reduce secondary microthrombin in the penumbra, improve regional blood flow, reduce ischemic lesions and ameliorate neurological deficits via the inhibition of circulating and clot-bound thrombin, platelet aggregation, and vascular contraction 3,13,14,24) . The nationale for the early administration of antithrombotic drugs is to prevent propagation of an acute thrombosis and recurrent embolism 23) .…”

“…There was no death of patient involved in this study. The median NIHSS was 8.0 (range, [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] at admission, 4.1 (range, 0-18) upon discharge, and 3.3 (range, 0-17) after three months. A good outcome was achieved in 65 patients (81%) upon discharge and in 71 patients (88%) after three months.…”

“…Argatroban is a selective direct thrombin inhibitor that has recently been used in the treatment of AIS and it has been approved in Japan and Korea as a treatment option for non-lacunar subtype-AIS presenting within 48 hours of ischemic symptom onset 3,14) . Argatroban has the potential to reduce secondary microthrombin in the penumbra, improve regional blood flow, reduce ischemic lesions and ameliorate neurological deficits 3,13,14,24) .…”

“…Argatroban has the potential to reduce secondary microthrombin in the penumbra, improve regional blood flow, reduce ischemic lesions and ameliorate neurological deficits 3,13,14,24) . It has been shown in many previous clinical and animal studies that this drug is effective for AIS patients without increasing intracranial hemorrhage 3,9,[11][12][13][14][15][16]24) . In this study, we performed IV argatroban in patients with AIS presenting beyond six hours of ischemic symptom onset in order to analyze the efficacy and safety of this drug.…”