Argatroban

Abstract

Argatroban, a highly selective direct thrombin inhibitor, is indicated for use as an anticoagulant for the treatment and prophylaxis of thrombosis in patients with heparin-induced thrombocytopenia (HIT), and in patients undergoing percutaneous coronary intervention (PCI) who have, or are at risk for, HIT. Intravenous argatroban improved clinical outcomes and was generally well tolerated in adults with HIT or HIT with thrombosis syndrome (HITTS). In two pivotal, open-label, historically controlled studies in adults with HIT, the incidence of the primary composite endpoint (all-cause death, all-cause amputation, or new thrombosis) was significantly lower in argatroban recipients than in historical controls, and more argatroban recipients than historical controls stayed event-free during the study according to a Kaplan-Meier analysis. In adults with HITTS in these trials, although the incidence of the primary composite endpoint did not differ significantly between argatroban recipients and historical controls, a Kaplan-Meier analysis showed that more patients receiving argatroban than historical controls remained event-free during the study. Major and minor bleeding rates in argatroban recipients were generally similar to those in historical controls in these studies. Argatroban was also an effective anticoagulant in patients with HIT undergoing PCI in three small, uncontrolled trials, pooled data from which showed that most (>or=95%) patients achieved a satisfactory outcome of the PCI procedure and adequate anticoagulation (coprimary endpoints). It was generally well tolerated in these patients, with the incidence of major bleeding being <or=1.1%. The efficacy and safety of argatroban in pediatric patients has not been established. However, a small uncontrolled, preliminary study suggests that it may be useful in seriously ill pediatric patients requiring nonheparin anticoagulation.

Advances in the reduction of quinolines to 1,2,3,4‐tetrahydroquinolines

“…Acting as pharmacodynamics targets . Some tetrahydroquinolines acting on ion channels compounds 25 – 27 [180–183] (Figure 5), membrane receptors compounds 28 – 35 [184–194] (Figure 6), steroid hormone receptors compounds 36 – 46 [21,195–205] (Figure 7), and nonsteroid hormone receptors compounds 47–54 [206–224] (Figure 8).…”

Evaluation of the Use of Argatroban or Bivalirudin for the Management of Suspected Heparin-Induced Thrombocytopenia in the Setting of Continuous Renal Replacement Therapy

“…4 Intravenous direct thrombin inhibitors (DTIs) bivalirudin and argatroban have been studied for the treatment of HIT, but there is minimal literature regarding the use of these agents in patients on CRRT. [5][6][7] CRRT with no anticoagulation has been shown to provide adequate filter life in some patients with high bleeding risk on CRRT, 8 but untreated HIT carries approximately 50% risk of thrombosis. 9 The purpose of this study was to investigate the current management of anticoagulation in patients with suspected HIT while on CRRT and to identify bleeding and thromboembolic…”

Novel degradation products of argatroban: Isolation, synthesis and extensive characterization using NMR and LC-PDA-MS/Q-TOF

“…Argatroban has a small molecular weight and thus it enters into thrombus and directly inactivates the thrombin already combined with fibrin thrombus, and even exhibits an antithrombotic effect against an early formed thrombosis. Argatroban is given intravenously and the drug plasma concentration reaches steady state in 1–3 h [2] .

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