Detail of "120993-53-5"

Reference

Distinct effects of recombinant desulfatohirudin (Revasc) and heparin on plasma levels of fibrinopeptide A and prothrombin fragment F1

Distinct effects of recombinant desulfatohirudin (Revasc) and heparin on plasma levels of fibrinopeptide A and prothrombin fragment F1.2 in unstable angina: A multicenter trial. Rao, A. Koneti; Sun, Ling; Chesebro, James H.; Fuster, Valentin; Harrington, Robert A.In this study， 120993-53-5 and 9002-04-4 are also used.; Schwartz, Darryl; Gallo, Paul; Matos, Deborah; Topol, Eric J. (School Medicine, Temple University, Philadelphia, PA 19140, USA). Circulation, 94(10), 2389-2395 (English) 1996 American Heart Association. CODEN: CIRCAZ. ISSN: 0009-7322. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Thrombin plays an important role in the pathogenesis of acute coronary thrombosis. We studied the effects of a direct thrombin inhibitor, recombinant desulfatohirudin, and heparin on plasma levels (at 0, 4, 12, and 24 h) of fibrinopeptide A (FPA), which reflects thrombin action, and prothrombin fragment F1.2, which reflects thrombin generation, in patients with unstable angina. Patients were randomized to one of two doses of heparin (n=50) (target activated partial thromboplastin time, 65 to 90 s or 90 to 110 s) or one of four doses of r-hirudin (n=113) (0.05, 0.10, 0.20, or 0.30 mg?kg-1?h-1 by infusion). R-Hirudin induced a dose-dependent decline in plasma FPA. At 24 h, FPA levels with 0.1- to 0.3- mg?kg-1?h-1 r-hirudin regimens were significantly lower than with 0.05 mg?kg-1?h-1 r-hirudin; levels with 0.1- to 0.2- mg?kg-1?h-1 r-hirudin regimens were lower than with both heparin regimens. Plasma F1.2 did not decline significantly during therapy with heparin or hirudin except at 0.3 mg?kg-1?h-1 hirudin. At 24 h, they were higher with the 0.05-mg?kg-1?h-1 r-hirudin regimen than with other regimens. For comparable levels of thrombin generation (F1.2 levels), FPA levels were higher in heparin patients than in hirudin patients. For the same FPA values, the corresponding F1.2 values were higher in the hirudin group. Our findings provide evidence for distinct in vivo effects of the two agents and suggest that r-hirudin is a relatively more potent inhibitor of thrombin action but a less effective inhibitor of thrombin generation than heparin. The lower FPA levels in hirudin patients may reflect its ability to inactivate clot-bound thrombin. The relative clin. efficacies of the two agents need to be defined by clin. trials in progress. .

Direct thrombin inhibitors

Direct thrombin inhibitors. Kaplan, Karen L. (601 Elmwood Avenue, Department of Medicine, Hematology-Oncology Unit, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA). Expert Opinion on Pharmacotherapy, 4(5), 653-666 (English) 2003 Ashley Publications Ltd. CODEN: EOPHF7. ISSN: 1465-6566. DOCUMENT TYPE: Journal; General Review CA Section: 1 (Pharmacology) A review. This review deals with a newly-developed category of antithrombotic drugs - the direct thrombin inhibitors. These agents interact with thrombin and block its catalytic activity on fibrinogen, platelets and other substrates. Heparin and its derivs. (low mol. wt. heparins and the active pentasaccharide) inhibit thrombin and/or other coagulation serine proteases indirectly via antithrombin, and the warfarin-type drugs interfere with the synthesis of the precursors of the coagulation serine proteases. 120993-53-5 and 8001-27-2 are also in the experiment. The direct thrombin inhibitors approved for clin. use at present (lepirudin, desirudin, bivalirudin, argatroban) and another in the advanced clin. testing stage (melagatran/ximelagatran), are the subject of this review. The chem. structure; kinetics of thrombin inhibition; pharmacokinetics and clin. use of each of these is discussed. .