Document Detail

Ximelagatran: an orally active direct thrombin inhibitor.
MedLine Citation:
PMID:  15998925     Owner:  NLM     Status:  MEDLINE    
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.
Michael P Gulseth
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists     Volume:  62     ISSN:  1079-2082     ISO Abbreviation:  Am J Health Syst Pharm     Publication Date:  2005 Jul 
Date Detail:
Created Date:  2005-07-06     Completed Date:  2005-11-15     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9503023     Medline TA:  Am J Health Syst Pharm     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1451-67     Citation Subset:  IM    
University of Minnesota College of Pharmacy/Saint Mary's Medical Center, 344 Kirby Plaza, 1208 Kirby Drive, Duluth, MN 55812, USA.
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MeSH Terms
Anticoagulants / adverse effects,  pharmacokinetics,  therapeutic use*
Atrial Fibrillation / complications
Azetidines / adverse effects,  pharmacokinetics,  therapeutic use*
Biological Availability
Clinical Trials, Phase III as Topic
Drug Interactions
Metabolic Clearance Rate
Stroke / etiology,  prevention & control
Thrombin / antagonists & inhibitors*
Thromboembolism / prevention & control
Venous Thrombosis / prevention & control
Warfarin / adverse effects,  therapeutic use
Reg. No./Substance:
0/Anticoagulants; 0/Azetidines; 0/Benzylamines; 0/ximelagatran; 81-81-2/Warfarin; EC
Comment In:
Am J Health Syst Pharm. 2005 Jul 15;62(14):1449   [PMID:  15998924 ]

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