Direct thrombin inhibitors.
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 derivatives (low molecular weight 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. The direct thrombin inhibitors approved for clinical use at present (lepirudin, desirudin, bivalirudin, argatroban) and another in the advanced clinical testing stage (melagatran/ximelagatran), are the subject of this review. The chemical structure; kinetics of thrombin inhibition; pharmacokinetics and clinical use of each of these is discussed.
Hematology-Oncology Unit, Department of Medicine, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Box 610, Rochester, NY 14642, USA. karen_kaplan@urmc.rochester.edu
Karen L
KL
Kaplan
D000991:Antithrombins / Q000493:pharmacokinetics / Q000627:therapeutic use; D001120:Arginine / Q000031:analogs & derivatives; D003327:Coronary Disease / Q000188:drug therapy; D006207:Half-Life; D006629:Hirudins / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D008657:Metabolic Clearance Rate; D010446:Peptide Fragments / Q000493:pharmacokinetics / Q000494:pharmacology; D010875:Pipecolic Acids / Q000493:pharmacokinetics / Q000494:pharmacology; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000494:pharmacology; D013449:Sulfonamides; D013917:Thrombin / Q000187:drug effects / Q000502:physiology*; D020246:Venous Thrombosis / Q000188:drug therapy
D000991:Antithrombins; D006629:Hirudins; D010446:Peptide Fragments; D010875:Pipecolic Acids; D011994:Recombinant Proteins; D013449:Sulfonamides; D001120:Arginine; D013917:Thrombin; C031942:argatroban; C074619:bivalirudin