Ximelagatran: an oral direct thrombin inhibitor.
OBJECTIVE
To present the chemistry, pharmacology, and pharmacokinetics of ximelagatran, an oral direct thrombin inhibitor (DTI), and to review available comparative clinical trial data evaluating its efficacy and safety relative to other antithrombotic agents in the prevention and treatment of thromboembolism.


METHODS
A search of the PubMed and Cochrane databases (1995-August 2004), supplemented by a manual search of article bibliographies, conference abstracts, and data on file from the manufacturer, was conducted. Key search terms were ximelagatran, melagatran, H376/95, and direct thrombin inhibitors.


METHODS
Pertinent information from available clinical trials, including study design, patient demographics, dosing regimens, anticoagulant comparators, methods for evaluating effectiveness, treatment outcomes, adverse events, and pharmacokinetic and pharmacodynamic evaluations, was extracted.


RESULTS
Ximelagatran is an orally administered DTI under development for use in the treatment of venous thromboembolism (VTE), long-term prevention of a second VTE event, stroke secondary to atrial fibrillation, prevention of VTE after orthopedic procedures, and recurrent ischemic events after acute myocardial infarction.


CONCLUSIONS
Ximelagatran, in twice-daily doses of 24 or 36 mg, is an alternative to low-molecular-weight heparins or warfarin in thromboprophylaxis following orthopedic knee replacement, atrial fibrillation, or initial treatment of VTE. Improved outcomes versus placebo were seen in the long-term prevention of VTE in patients who completed an initial 6 months of treatment. Liver-related effects need further clarification.
Dager
William E
WE
Department of Pharmaceutical Services, University of California Davis Medical Center, Sacramento, CA, USA. william.dager@ucdmc.ucdavis.edu
Vondracek
Thomas G
TG
McIntosh
Bruce A
BA
Nutescu
Edith A
EA
D000328:Adult; D000925:Anticoagulants / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use; D019540:Area Under Curve; D019644:Arthroplasty, Replacement, Hip; D019645:Arthroplasty, Replacement, Knee; D001384:Azetidines / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use; D001596:Benzylamines; D001682:Biological Availability; D002986:Clinical Trials as Topic; D018565:Food-Drug Interactions; D006207:Half-Life; D006801:Humans; D008297:Male; D020246:Venous Thrombosis / Q000188:drug therapy*
D000925:Anticoagulants; D001384:Azetidines; D001596:Benzylamines; C426686:ximelagatran