Novel uses for current and future direct thrombin inhibitors: focus on ximelagatran and bivalirudin.
Ximelagatran and bivalirudin are direct thrombin inhibitors that have been studied for the prevention and treatment of thrombosis and have potential advantages over the traditional indirect thrombin inhibitors (i.e., warfarin, unfractionated heparin and low molecular-weight heparin). They are both reversible inhibitors of thrombin and block both circulating and fibrin-bound thrombin. Ximelagatran and bivalirudin possess favourable pharmacokinetic and pharmacodynamic profiles including wider therapeutic indices, faster onsets of action and less interpatient variability compared to indirect thrombin inhibitors. Ximelagatran has shown favourable clinical trial results in venous thromboembolism prophylaxis and atrial fibrillation. Similarly, bivalirudin has shown positive results in patients with acute coronary syndromes, however, further investigation is needed. Ximelagatran and bivalirudin have shown promising results in the management of thrombosis and the results of future studies confirming their use for the aforementioned indications are anticipated.
Kalus
James S
JS
College of Pharmacy, Department of Pharmacy Practice, University of Rhode Island, Providence, RI, USA. mcaron@uri.edu
Caron
Michael F
MF
D000208:Acute Disease; D000284:Administration, Oral; D000991:Antithrombins / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D001384:Azetidines / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D001596:Benzylamines; D017326:Clinical Trials, Phase III as Topic; D003327:Coronary Disease / Q000188:drug therapy; D004311:Double-Blind Method; D006629:Hirudins / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D013577:Syndrome; D013927:Thrombosis / Q000188:drug therapy / Q000517:prevention & control
D000991:Antithrombins; D001384:Azetidines; D001596:Benzylamines; D006629:Hirudins; D010446:Peptide Fragments; D011994:Recombinant Proteins; C426686:ximelagatran; C074619:bivalirudin