HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gulseth, M. P. Search for Related Content PubMed PubMed Citation Articles by Gulseth, M. P.

MICHAEL P. GULSETH, PHARM.D., BCPS, is Assistant Professor/Clinical Coordinator, University of Minnesota College of Pharmacy/Saint Mary’s Medical Center, 344 Kirby Plaza, 1208 Kirby Drive, Duluth, MN 55812 (mgulseth{at}umn.edu).

Purpose. The chemistry, pharmacology, pharmacokinetics, clinical efficacy, dosage and administration, contraindications, and adverse effects of ximelagatran are reviewed. Summary. Ximelagatran is the first orally active direct thrombin inhibitor to be tested in Phase III clinical trials. After oral administration, ximelagatran is rapidly converted to its active metabolite, melagatran. Melagatran (after oral ximelagatran administration) predictably inhibits thrombin function without need for routine anticoagulation monitoring. Melagatran effectively inhibits both free and clot-bound thrombin—a potential pharmacodynamic advantage over heparin products. Melagatran has a half-life of 2.4–4.6 hours, necessitating twice-daily administration. Melagatran is primarily eliminated by the kidneys and has not been studied clinically in patients with severe renal failure. Ximelagatran has undergone 10 Phase III trials (6 for prophylaxis of venous thromboembolism [VTE] due to orthopedic surgery, 1 for initial treatment of VTE, 1 for long-term prevention of VTE recurrence, and 2 for stroke prophylaxis due to atrial fibrillation). Results were generally positive. AstraZeneca applied in December 2003 for marketing approval of ximelagatran for prevention of VTE after total knee replacement surgery, long-term prevention of VTE recurrence after standard therapy, and stroke prevention due to atrial fibrillation. FDA denied approval of ximelagatran for all indications, mainly because of increased rates of coronary artery disease events in ximelagatran recipients in some studies and the possibility of hepatic failure when the medication is used for long-term therapy. Conclusion. Ximelagatran has shown promise as a possible alternative to warfarin and other anticoagulants but will require further study to ensure its safety. Index terms: Anticoagulants; Contraindications; Dosage; Dosage schedules; Drug administration; Drugs; Excretion; Half-life; Melagatran; Metabolism; Pharmacokinetics; Toxicity; Ximelagatran

 

This article has been cited by other articles:

				F. Rogers, J. A. Rebuck, and R. F. Sing Venous Thromboembolism in Trauma: An Update for the Intensive Care Unit Practitioner J Intensive Care Med, January 1, 2007; 22(1): 26 - 37. [Abstract] [PDF]

				E. A. Nutescu, A. K. Wittkowsky, and W. E. Dager Uncertain times for oral anticoagulation therapy Am. J. Health Syst. Pharm., July 15, 2005; 62(14): 1449 - 1449. [Full Text] [PDF]