Direct thrombin inhibitors

Direct thrombin inhibitors interact with thrombin and block its catalytic activity on a wide range of substrates. Their action is in contrast to heparin and its derivatives, which inhibit thrombin and other coagulation serine proteases via antithrombin, and to the warfarin-type drugs that interfere with synthesis of the precursors of the coagulation serine proteases. There are three direct thrombin inhibitors approved for clinical use at present (lepirudin, bivalirudin, argatroban) and another in advanced clinical testing (melagatran/ximelagatran). The chemical structure, kinetics of thrombin inhibition, pharmacokinetics, and clinical use of each of these agents are discussed.