Ximelagatran

Drugs of Today

Volumn 42, Issue 1, 2006, Pages 3-19

  Choudhury, Anirban ^a   Goyal, Deepak ^a   Lip, Gregory Y H ^a  

^a UNIVERSITY DEPARTMENT OF MEDICINE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLSALICYLIC ACID; ALANINE AMINOTRANSFERASE; AMIODARONE; ANTICOAGULANT AGENT; ANTIVITAMIN K; ARGATROBAN; DALTEPARIN; ENOXAPARIN; FLUCLOXACILLIN; HEPARIN; LEPIRUDIN; LOW MOLECULAR WEIGHT HEPARIN; MELAGATRAN; SERINE PROTEINASE; THROMBIN; THROMBIN INHIBITOR; WARFARIN; XIMELAGATRAN;

ABNORMALLY HIGH SUBSTRATE CONCENTRATION IN BLOOD; ACUTE CORONARY SYNDROME; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ANTICOAGULANT THERAPY; BLEEDING; CEREBROVASCULAR ACCIDENT; CLINICAL TRIAL; DEEP VEIN THROMBOSIS; DOSE RESPONSE; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG COST; DRUG EFFICACY; DRUG HALF LIFE; DRUG POTENTIATION; DRUG SAFETY; DRUG TOLERABILITY; GALLSTONE; HEART ATRIUM FIBRILLATION; HEART INFARCTION; HEPARIN INDUCED THROMBOCYTOPENIA; HEPATITIS B; HUMAN; JAUNDICE; KIDNEY DYSFUNCTION; LIVER DYSFUNCTION; LIVER METASTASIS; LUNG EMBOLISM; MEDICAL PRACTICE; META ANALYSIS; REVIEW; STROKE; SYSTEMATIC REVIEW; THROMBOEMBOLISM; THROMBOSIS; TRANSIENT ISCHEMIC ATTACK; VENOUS THROMBOEMBOLISM;

ADMINISTRATION, ORAL; ANTICOAGULANTS; AZETIDINES; BENZYLAMINES; CEREBROVASCULAR ACCIDENT; DRUG ADMINISTRATION SCHEDULE; HUMANS; MYOCARDIAL INFARCTION; RANDOMIZED CONTROLLED TRIALS; RECURRENCE; THROMBIN; THROMBOEMBOLISM; VENOUS THROMBOSIS; WARFARIN;

EID: 33645073008     PISSN: 16993993     EISSN: 16994019     Source Type: Journal    
DOI: 10.1358/dot.2006.42.1.893611     Document Type: Review

References (72)

1. Maly, J., Pecka, M., Vodickova, L. et al. Changes in the activity of thrombocytes by smoking. Sb Ved Pr Lek Fak Karlovy Univerzity Hradci Kralove 1990, 33: 325-33.
2. Mustard, J.F., Packham, M.A., Rowsell, H.C., Jorgensen, L. The role of thrombogenic factors in atherosclerosis. Ann NY Acad Sci 1968, 149: 848-59.
3. Mustard, J.F., Packham, M.A. The role of blood and platelets in atherosclerosis and the complications of atherosclerosis. Thromb Diath Haemorrh 1975, 33: 444-56.
4. Tschoepe, D., Roesen, P., Esser, J. et al. Large platelets circulate in an activated state in diabetes mellitus. Semin Thromb Hemost 1991, 17: 433-8.
5. Clagett, G.P., Anderson, F.A. Jr., Geerts, W. et al. Prevention of venous thromboembolism. Chest 1998, 114 (5 Suppl.): 531S-60S.
6. Kannel, W.B., Abbott, R.D., Savage, D.D. et al. Epidemiological features of chronic atrial fibrillation: The Framingham study. N Engl J Med 1982, 306: 1018-22.
7. Albers, G.W., Dalen, J.E., Laupacis, A., Manning, W.J., Petersen, P., Singer, D.E. Antithrombotic therapy in atrial fibrillation. Chest 2001, 119: 194S-206S.
8. Wattigney, W.A., Mensah, G.A., Croft, J.B. Increasing trends in hospitalization for atrial fibrillation in the United States, 1985 through 1999: Implications for primary prevention. Circulation 2003, 108: 711-6.
9. Murray, C.J.L., Lopez, A.D., Mathers, C.D., Stein, C. The global burden of disease 2000 project: Aims, methods and data sources. Global Programme on Evidence for Health Policy - Discussion Papers, No. 36. World Health Organization, Geneva 2001.
10. Atrial fibrillation as a contributing cause of death and Medicare hospitalization - United States, 1999. MMWR 2003, 52: 128-31.
11. Public health and aging: Hospitalizations for stroke among adults aged >/=65 years - United States, 2000. MMWR 2003, 52: 586-9.
12. Wolf, P.A., Abbott, R.D., Kannel, W.B. Atrial fibrillation as an independent risk factor for stroke: The Framingham study. Stroke 1991, 22: 983-8.
13. Karatas, M., Dilek, A., Erkan, H., Yavuz, N., Sozay, S., Akman, N. Functional outcome in stroke patients with atrial fibrillation. Arch Phys Med Rehabil 2000, 81: 1025-9.
14. Dulli, D.A., Stanko, H., Levine, R.L. Atrial fibrillation is associated with severe acute ischemic stroke. Neuroepidemiology 2003, 22: 118-23.
15. Hart, R.G., Palacio, S., Pearce, L.A. Atrial fibrillation, stroke, and acute antithrombotic therapy: Analysis of randomized clinical trials. Stroke 2002, 33: 2722-7.
16. Hart, R.G., Benavente, O., McBridge, R. et al. Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: A meta-analysis. Ann Intern Med 1999, 131: 492-501.
17. Antithrombotic Trialists' Collaboration. Collaborative analysis of randomised trials of anti platelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002, 324: 71-86.
18. Bo, S., Ciccone, G., Scaglione, L. et al. Warfarin for non-valvar atrial fibrillation: Still under-used in the 21st century? Heart 2003, 89: 553-4.
19. Peterson, G.M., Boom, K., Jackson, S.L., Vial, J.H. Doctors' beliefs on the use of antithrombotic therapy in atrial fibrillation: Identifying barriers to stroke prevention. Intern Med J 2002, 32: 15-23.
20. Brouwer, M.A., Verheugt, RW. Oral anticoagulation for acute coronary syndromes. Circulation 2002, 105: 1270-4.
21. Anand, S.S., Yusuf, S. Oral anticoagulants in patients with coronary artery disease. J Am Coll Cardiol 2003, 41 (4 Suppl. S): 62S-9S.
22. Ortel, T.L., Chong, B.H. New treatment options for heparin-induced thrombocytopenia. Semin Hematol 1998; 35: 26-34.
23. Lewis, B.E., Wallis, D.E., Berkowitz, S.D. et al. Argatroban anticoagulant therapy in patients with heparin-induced thrombocytopenia. Circulation 2001, 103: 1838-43.
24. Brady, S.F., Stauffer, K.J., Lumma, W.C. et al. Discovery and development of the novel potent orally active thrombin inhibitor N-(9-hydroxy-9- fluorenecarboxy)prolyl trans-4-aminocyclohexylmethyl amide (L-372,460): Coapplication of structure-based design and rapid multiple analogue synthesis on solid support. J Med Chem 1998, 41: 401-6.
25. McClanahan, T.B., Hicks, G.W., Ignasiak, D.P. et al. The antithrombotic effects of CI-1028, an orally bioavailable direct thrombin inhibitor, in a canine model of venous and arterial thrombosis. J Thromb Thrombolysis 2000, 10: 277-84.
26. Oh, Y.S., Yun, M., Hwang, S.Y. et al. Discovery of LB30057, a benzamidrazone-based selective oral thrombin inhibitor. Bioorg Med Chem Lett 1998, 8: 631-4.
27. Mungall, D. BIBR-1048 Boehringer Ingelheim. Curr Opin Investig Drugs 2002, 3: 905-7.
28. Gustafsson, D. Oral direct thrombin inhibitors in clinical development. J Intern Med 2003, 254: 322-34.
29. Eriksson, U.G., Bredberg, U., Hoffmann, K.J. et al. Absorption, distribution, metabolism and excretion of ximelagatran, an oral direct thrombin inhibitor, in rats, dogs and humans. Drug Metab Dispos 2003, 31: 294-305.
30. Gustafsson, D., Nystrom, J., Carlsson, S. et al. The direct thrombin inhibitor melagatran and its oral prodrug H 376/95: Intestinal absorption properties, biochemical and pharmacodynamic effects. Thromb Res 2001, 101: 171-81.
31. Eriksson, U.G., Bredberg, U., Gislen, K. et al. Pharmacokinetics and pharmacodynamics of ximelagatran, a novel oral direct thrombin inhibitor, in young healthy male subjects. Eur J Clin Pharmacol 2003, 59: 35-43.
32. Johansson, L.C., Frison, L., Logren, U., Fager, G., Gustafsson, D., Eriksson, U.G. Influence of age on the pharmacokinetics and pharmacodynamics of ximelagatran, an oral direct thrombin inhibitor. Clin Pharmacokinet 2003, 42: 381-92.
33. Sarich, T.C., Teng, R., Peters, G.R. et al. No influence of obesity on the pharmacokinetics and pharmacodynamics of melagatran, the active form of the oral direct thrombin inhibitor ximelagatran. Clin Pharmacokinet 2003, 42: 485-92.
34. Johansson, L., Andersson, M., Fager, G., Gustafsson, D., Eriksson, U. No influence of ethnic origin on the pharmacokinetics and pharmacodynamics of melagatran following oral administration of ximelagatran, a novel oral direct thrombin inhibitor, to healthy male volunteers. Clin Pharmacokinet 2003, 42: 475-84.
35. Frydman, A. Low molecular weight heparins: An overview of their pharmacodynamics, pharmacokinetics and metabolism in humans. Haemostasis 1996, 26 (Suppl. 2): 24-38.
36. Dunn, C.J., Jarvis, B. Daltepirin: An update on its pharmacological properties and clinical efficacy in the prophylaxis and treatment of thromboembolic disease. Drugs 2000, 60: 203-37.
37. Bredberg, E., Andersson, T.B., Frison, L. et al. Ximelagatran, an oral direct thrombin inhibitor, has a low potential for cytochrome P450-mediated drug-drug interactions. Clin Pharmacokinet 2003, 42: 765-77.
38. Teng, R., Sarich, T.C., Eriksson, U.G. et al. A pharmacokinetic study of the combined administration of amiodarone and ximelagatran, an oral direct thrombin inhibitor. J Clin Pharmacol 2004, 44: 1063-71.
39. Fager, G., Cullberg, M., Eriksson-Lepkowska, M., Frison, L., Eriksson, U.G. Pharmacokinetics and pharmacodynamics of melagatran, the active form of the oral direct thrombin inhibitor ximelagatran, are not influenced by acetylsalicylic acid. Eur J Clin Pharmacol 2003, 59: 283-9.
40. Eriksson, U.G., Johansson, S., Attman, P.O. et al. Influence of severe renal impairment on the pharmacokinetics and pharmacodynamics of oral ximelagatran and subcutaneous melagatran. Clin Pharmacokinet 2003, 42: 743-53.
41. Wahlander, K., Eriksson-Lepkowska, M., Frison, L. et al. No influence of mild-to-moderate hepatic impairment on the pharmacokinetics and pharmacodynamics of ximelagatran, an oral direct thrombin inhibitor. Clin Pharmacokinet 2003, 42: 755-64.
42. Bååthe, S., Hamrén, B., Karlsson, M.O. et al. Population pharmacokinetics of melagatran, the active form of the oral direct thrombin inhibitor ximelagatran, in atrial fibrillation patients receiving long-term anticoagulation therapy. Clin Pharmacokinet 2006, in press.
43. Eriksson, U.G., Baathe, S., Hamrén, B., Wollbratt, M., Wolzt, M., Grind, M. Predictable pharmacokinetics of ximelagatran, an oral direct thrombin inhibitor, in nonvalvular atrial fibrillation patients receiving long-term treatment. Pathophysiol Haemost Thromb 2002, 32: 56.
44. Gustafsson, D., Antonsson, T., Bylund, R. et al. Effects of melagatran, a new low-molecular-weight thrombin inhibitor, on thrombin and fibrinolytic enzymes. Thromb Haemost 1998, 79: 110-8.
45. Boström, S.L., Hansson, G.R, Kjaer, M. et al. Effects of melagatran, the active form of the oral direct thrombin inhibitor ximelagatran, and dalteparin on the endogenous thrombin potential in venous blood from healthy male subjects. Blood Coagul Fibrinolysis 2003, 14: 457-62.
46. Nylander, S., Mattson, C. Thrombin-induced platelet activation and its inhibition by anti-coagulants with different modes of action. Blood Coagul Fibrinolysis 2003, 14: 159-67.
47. Mattson, C., Menschik-Lundin, A., Nylander, S. et al. Effects of different types of thrombin inhibitors on thrombin/thrombomodulin modulated activation of protein C in vitro. Thromb Res 2001, 104: 475-86.
48. Hirsh, J., Dalen, J.E., Anderson, D.R. et al. Oral anticoagulants: Mechanism of action, clinical effectiveness and optimal therapeutic range. Chest 2001, 119 (Suppl.): 8S-21S.
49. Mattson, C., Bjorkman, J.A., Abrahamsson, T. et al. Local proCPU (TAF1) activation during thrombolytic treatment in a dog model of coronary artery thrombosis can be inhibited with a direct, small molecule thrombin-inhibitor (melegatran). Thromb Haemost 2002, 87: 557-62.
50. Mattson, C., Bjorkman, J.A., Ulvinge, J.C. et al. Melagatran, hirudin and heparin as adjuncts to tissue-type plasminogen activator in the canine model of coronary artery thrombolysis. Fibrinolysis Proteolysis 1997, 11: 121-8.
51. Sarich, T.C., Wolzt, M., Eriksson, U.G. et al. Effects of ximelagatran, an oral direct thrombin inhibitor, r-hirudin and enoxaparin on thrombin generation and platelet activation in healthy male subjects. J Am Coll Cardiol 2003, 41: 557-64.
52. Kamath, S., Blann, A.D., Caine, G.J., Gurney, D., Chin, B.S., Lip, G.Y. Platelet P-selectin levels in relation to plasma soluble P-selectin and beta-thromboglobulin levels in atrial fibrillation. Stroke 2002, 33: 1237-42.
53. Wolzt, M., Boström, S.L., Svensson, M., Wåhlander, K., Grind, M., Sarich, T.C. Effects of the oral direct thrombin inhibitor ximelagatran on P-selectin expression and thrombin generation in atrial fibrillation. Pathophysiol Haemost Thromb 2003, 33: 68-74.
54. Eriksson, B.I., Arfwidsson, A.C., Frison, L. et al. A dose ranging study of the oral direct thrombin inhibitor, ximelagatran and its subcutaneous form melagatran, compared with dalteparin in the prophylaxis of thromboembolism after hip or knee replacement. METHRO I. Thromb Haemost 2002, 87: 231-7.
55. Eriksson, B.I., Bergqkvist, D., Kalebo, P. et al. Ximelagatran and melagatran compared with dalteparin for the prevention of venous thromboembolism after total hip or knee replacement. The METHRO II randomised trial. Lancet 2002, 360: 1441-7.
56. Eriksson, B.I., Agnelli, G., Cohen, A.T. et al.; METHRO III Study Group. Direct thrombin inhibitor melagatran followed by oral ximelagatran in comparison with enoxaparin for prevention of venous thromboembolism after total hip or knee replacement. Thromb Haemost 2003, 89: 288-96.
57. Eriksson, B.I., Agnelli, G., Cohen, A.T. et al. The direct thrombin inhibitor melagatran followed by oral ximelagatran compared with enoxaparin for the prevention of venous thromboembolism after total hip or knee replacement: The EXPRESS study. Thromb Haemost 2003, 1: 2474-6.
58. Francis, C.W., Berkowitz, S.D., Comp, P.C. et al. Comparison of ximelagatran with warfarin for the prevention of venous thromboembolism after total knee replacement. N Engl J Med 2003, 349: 1703-12.
59. Colwell, C.W. Jr., Berkowitz, S.D., Lieberman, J.R. et al. Oral direct thrombin inhibitor ximelagatran compared with warfarin for the prevention of venous thromboembolism after total knee arthroplasty. J Bone Joint Surg Am 2005, 87: 2169-77.
60. Schulman, S., Wåhlander, K., Lundström, T., Billing Clason, S., Eriksson, H., for the THRIVE III Investigators. Secondary prevention of venous thromboembolism with the oral direct thrombin inhibitor ximelagatran. N Engl J Med 2003, 349: 1713-21.
61. Fiessinger, J.N., Huisman, M.V., Davidson, B.L. et al.; THRIVE Treatment Study Investigators. Ximelagatran vs low-molecular-weight heparin and warfarin for the treatment of deep vein thrombosis: a randomized trial. JAMA 2005, 293: 681-9.
62. Petersen, P., Grind, M., Adler, J. Ximelagatran versus warfarin for stroke prevention in patients with nonvalvular atrial fibrillation. SPORTIF II: A dose-guiding, tolerability, and safety study. J Am Coll Cardiol 2003, 41: 1445-51.
63. Petersen, P. A 2-year follow-up of ximelagatran as an oral anticoagulant for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Neurology 2002, 58: A477.
64. Executive Steering Committee on behalf of the SPORTIF III Investigators. Stroke prevention with the oral direct thrombin inhibitor ximelagatran compared with warfarin in patients with non-valvularatrial fibrillation (SPORTIF III): Randomised controlled trial. Lancet 2003, 362: 1691-8.
65. Albers, G.W., Diener, H.C., Frison, L. et al.; SPORTIF Executive Steering Committee for the SPORTIF V Investigators. Ximelagatran vs warfarin for stroke prevention in patients with nonvalvular atrial fibrillation: a randomized trial. JAMA 2005, 293: 690-8.
66. Wallentin, L., Wilcox, R.G., Weaver, W.D. et al. Oral ximelagatran for secondary prophylaxis after myocardial infarction: The ESTEEM randomised controlled trial. Lancet 2003; 362: 789-97.
67. Francis, C.W., Davidson, B.L., Berkowitz, S.D. et al. Ximelagatran versus warfarin for the prevention of venous thromboembolism after total knee arthroplasty. Ann Intern Med 2002; 137: 648-55.
68. Fuster, V., Ryden, L.E., Asinger, R.W. et al. ACC/ AHA/ESC guidelines for the management of patients with atrial fibrillation. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to develop guidelines for the management of patients with atrial fibrillation) developed in collaboration with the North American Society of Pacing and Electrophysiology. Eur Heart J 2001, 22: 1852-1923.
69. Halperin, J.L., and the Executive Steering Committee on behalf of the SPORTIF III and V Study Investigators. Ximelagatran compared with warfarin for prevention of thromboembolism in patients with nonvalvular atrial fibrillation: Rationale, objectives, and design of a pair of clinical studies and baseline patient characteristics (SPORTIF III and V). Am Heart J 2003, 146: 431-8.
70. Diener, H.C. Stroke prevention using the oral direct thrombin inhibitor ximelagatran in patients with non-valvular atrial fibrillation. Pooled analysis from the SPORTIF III and V studies. Cerebrovasc Dis 2006, 2: 279-93.
71. Budaj, A., Yusuf, S., Mehta, S.R. et al. Benefit of clopidogrel in patients with acute coronary syndromes without ST-segment elevation in various risk groups. Circulation 2002, 106: 1622-6.
72. Lee, W.M., Larrey, D., Olsson, R. et al. Hepatic findings in long-term clinical trials of ximelagatran. Drug Saf 2005, 28(4): 351-70.