Ximelagatran: a new oral anticoagulant.
Vitamin K antagonists are effective oral anticoagulants, but they have limitations related to a narrow therapeutic range, food and drug interactions, slow onset of action and the need for routine coagulation monitoring. Ximelagatran is a promising new oral anticoagulant under investigation in advanced clinical trials. It is a prodrug that is converted after oral administration to melagatran, a direct thrombin inhibitor, with a peak effect after 2 hours and a half-life of approximately 3 hours with primarily renal excretion. Administration results in prolongation of coagulation tests, but routine monitoring is not required because of reliable absorption and predictable effects. A large clinical trials program has demonstrated effectiveness in prophylaxis of deep vein thrombosis (DVT) following major orthopedic surgery, treatment of symptomatic DVT, prevention of embolism in patients with atrial fibrillation, and prophylaxis of recurrent events after acute myocardial infarction. Bleeding complications have been similar to those with standard therapy, with no unexpected adverse effects except for elevation of serum transaminase levels in over 6% of patients beginning after 1 month of therapy. Ximelagatran may be an alternative oral anticoagulant for patients currently taking vitamin K antagonists.
Francis
Charles W
CW
Hematology/Oncology Unit, School of Medicine and Dentistry, University of Rochester, 601 Elmwood Avenue, Box 610, Rochester, NY, USA. charles_francis@urmc.rochester.edu
D000925:Anticoagulants / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001384:Azetidines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001596:Benzylamines; D006331:Heart Diseases / Q000150:complications / Q000188:drug therapy / Q000517:prevention & control; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008111:Liver Function Tests; D020246:Venous Thrombosis / Q000150:complications / Q000188:drug therapy / Q000517:prevention & control
D000925:Anticoagulants; D001384:Azetidines; D001596:Benzylamines; C426686:ximelagatran