Dabigatran/Dabigatran Etexilate: Prevention of DVT prevention of ischemic stroke thrombin inhibitor

Drugs of the Future

Volumn 30, Issue 9, 2005, Pages 877-885

  Sorbera, L A ^a   Bozzo, J ^a   Castaner J ^a  

^a PROUS SCIENCE   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLSALICYLIC ACID; AZD 0837; D DIMER; DABIGATRAN; DABIGATRAN ETEXILATE; ENOXAPARIN; MCC 977; PANTOPRAZOLE; PEGMUSIRUDIN; SSR 182289; TGN 167; TGN 255; THROMBIN; THROMBIN INHIBITOR; UNCLASSIFIED DRUG; WARFARIN;

ANTICOAGULANT THERAPY; AREA UNDER THE CURVE; BLEEDING; DEEP VEIN THROMBOSIS; DOSE RESPONSE; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG ELIMINATION; DRUG HALF LIFE; DRUG MECHANISM; DRUG STRUCTURE; DRUG TOLERABILITY; EXPERIMENTAL RAT; FOOD DRUG INTERACTION; HEART ATRIUM FIBRILLATION; HEMATOMA; HUMAN; INTERNATIONAL NORMALIZED RATIO; MULTIPLE DRUG DOSE; NONHUMAN; PARTIAL THROMBOPLASTIN TIME; PROTHROMBIN TIME; RABBIT; REVIEW; RHESUS MONKEY; SINGLE DRUG DOSE; SYSTEMATIC REVIEW; THROMBIN TIME; TOTAL HIP PROSTHESIS; VENOUS THROMBOEMBOLISM; VOLUNTEER;

EID: 30544450381     PISSN: 03778282     EISSN: None     Source Type: Journal    
DOI: 10.1358/dof.2005.030.09.938760     Document Type: Review

References (41)

1. Hauel, N.H., Nar, H., Priepke, H., Ries, U.J., Stassen, J.M., Wienen, W. Structure-based design of novel potent nonpeptide thrombin inhibitors. J Med Chem 2002, 45: 1757-66.
2. Hauel, N., Priepke, H., Ries, U., Stassen, J.M., Wienen, W. (Boehringer Ingelheim Pharma KG). Disubstd. bicyclic heterocycles, their production and use as medicaments. DE 19706229, DE 19751939, EP 0966454, JP 2001509815, US 2003004181, US 6087380, US 6469039, US 6710055, WO 1998037075.
3. Walsh, RN. Platelet coagulation-protein interactions. Semin Thromb Hemost 2004, 30: 461-71.
4. Narayanan, S. Multifunctional roles of thrombin. Ann Clin Lab Sci 1999, 29: 275-80.
5. Heemskerk, J.W., Bevers, E.M., Lindhout, T. Platelet activation and blood coagulation. Thromb Haemost 2002, 88: 186-93.
6. Kahn, M.L., Nakanishi-Matsui, M., Shapiro, M.J., Ishihara, H., Coughlin, S.R. Protease-activated receptors 1 and 4 mediate activation of human platelets by thrombin. J Clin Invest 1999, 103: 879-87.
7. Trejo, J. Protease-activated receptors: New concepts in regulation of G protein-coupled receptor signaling and trafficking. J Pharmacol Exp Ther 2003, 307: 437-42.
8. Pineo, G.F., Hull, R.D. Unfractionated and low-molecular-weight heparin. Comparisons and current recommendations. Med Clin North Am 1998, 82: 587-99.
9. Kleinschmidt, K., Charles, R. Pharmacology of low molecular weight heparins. Emerg Med Clin North Am 2001, 19: 1025-49.
10. Weitz, J.I., Hudoba, M., Massel, D., Maraganore, J., Hirsh, J. Clot-bound thrombin is protected from inhibition by heparinantithrombin III but is susceptible to inactivation by antithrombin III-independent inhibitors. J Clin Invest 1990, 86: 385-91.
11. Hauptmann, J., Sturzebecher, J. Synthetic inhibitors of thrombin and factor Xa: From bench to bedside. Thromb Res 1999, 93: 203-41.
12. Tulinsky, A. Molecular interactions of thrombin. Semin Thromb Hemost 1996, 22: 117-24.
13. Das, J., Kimball, S.D. Thrombin active site inhibitors. Bioorg Med Chem 1995, 3: 999-1007.
14. Stassen, J.M., Hauel, N.H., Nar, H., Ries, U.J., Priepke, H.W.M., Wienen, W. Identification and in vitro characterization of BIBR 953 ZW, a novel synthetic low molecular weight direct thrombin inhibitor. 18th Cong Int Soc Thromb Haemost (July 6-12, Paris) 2001, Abst P755.
15. Stassen, J.M., Hauel, N.H., Nar, H., Ries, U.J., Priepke, H.M.W. Ex vivo anticoagulant activity of BIBR9532W, a novel synthetic direct thrombin inhibitor and of its prodrug BIBR1048 MS in different animal species. 18th Cong Int Soc Thromb Haemost (July 6-12, Paris) 2001, Abst P763.
16. Wienen, W., Nar, H., Ries, U.J., Priepke, H.W.M., Hauel, N.H., Stassen, J.M. Effects of the direct thrombin inhibitor BIBR953ZW and its orally active prodrug BIBR1048MS on experimentally-induced clot formation and template bleeding time in rats. 18th Cong Int Soc Thromb Haemost (July 6-12, Paris) 2001, Abst P761.
17. Wienen, W., Nar, H., Ries, U.J., Priepke, H.W.M., Hauel, N.H., Stassen, J.M. Antithrombotic effects of the direct thrombin inhibitor BIBR953ZW and its orally active prodrug BIBR1048MS in a model of venous thrombosis in rabbits. 18th Cong Int Soc Thromb Haemost (July 6-12, Paris) 2001, Abst OC853.
18. Busch, U., Schmid, J. Pharmacokinetics of the synthetic direct thrombin inhibitor BIBR 953 ZW in different animal species. 18th Cong Int Soc Thromb Haemost (July 6-12, Paris) 2001, Abst P766.
19. Stangier, J., Eriksson, B.I., Dahl, O.E., Ahnfelt, L., Nehmiz, G., Stahle, H., Rathgen, K., Svard, R. Pharmacokineticprofile of the oral direct thrombin inhibitor dabigatran etexilate in healthy volunteers and patients undergoing total hip replacement. J Clin Pharmacol 2005, 45: 555-63.
20. Slangier, J., Stahle, H., Rathgen, K. Seitz, Ch. Pharmacokinetics and pharmacodynamics of the direct thrombin inhibitor dabigatran in elderly healthy subjects. 20th Cong Int Soc Thromb Haemost (Aug 6-12, Sydney) 2005, Abst P22072E
21. Slangier, J., Rathgen, K., Gansser, D., Kohlbrenner, V., Stassen, J.M. Pharmacokinetics of BIBP 953 ZW, a novel low molecular weight direct thrombin inhibitor in healthy volunteers. 18th Cong Int Soc Thromb Haemost (July 6-12, Paris) 2001, Abst OC2347.
22. Slangier, J., Nehmiz, G., Reilly, P., Ezekowitz, M., Petersen, K.-E., Simmers, T., Wallentin, L. Pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran in a dose finding trial in atrial fibrillation. 20th Cong Int Soc Thromb Haemost (Aug 6-12, Sydney) 2005, Abst OR271.
23. Stassen, J.M., Rathgen, K., Zimmermann, R., Wienen, W., Slangier, J. Pharmacodynamics of the synthetic direct thrombin inhibitor BIBR953ZW in healthy subjects. 18th Cong Int Soc Thromb Haemost (July 6-12, Paris) 2001, Abst OC160.
24. Eriksson, B.I., Dahl, O.E., Ahnfelt, L., Kalebo, P., Slangier, J., Nehmiz, G., Hermansson, K., Kohlbrenner, V. Dose escalating safety study of a new oral direct thrombin inhibitor, dabigatran etexilate, in patients undergoing total hip replacement: BISTRO I. J Thromb Haemost 2004, 2(9): 1573-80.
25. Eriksson, B.I., Dahl, O.E., Buller, H.R., Hettiarachchi, R., Rosencher, N., Bravo, M.-L., Ahnfell, L., Piovella, R, Slangier, J., Kalebo, P., Reilly, P. A new oral direct thrombin inhibitor, dabigatran etexilate, compared with enoxaparin for prevention of thromboembolic events following total hip or knee replacement: The BISTRO II randomized trial. J Thromb Haemosl 2005, 3(1): 103-11.
26. Wallentin, L.C., Ezekowitz, M., Simmers, T.A., Pedersen, K.E., Slangier, J., Nehmiz, G., Reilly, P. Safety and efficacy of a new oral direct thrombin inhibitor dabigatran in atrial fibrillation - A dose finding trial with comparison to warfarin. Eur Soc Cardiol Cong (Sept 3-7, Stockholm) 2005, Abst P2949.
27. Boehringer Ingelheim Annual Report 2004.
28. Di Nisio, M., Middeldorp, S., Buller, H.R. Direct thrombin inhibitors. New Engl J Med 2005, 353(10): 1028-40.
29. Ezekowitz, M.D. Stroke prevention in atrial fibrillation: Anticoagulants and antithrombotics. Am Heart Hosp J 2004, 2(4, Suppl. 1): 31-5.
30. Stangier, J., Liesenfeld, K.H., Troconiz, Ch., Tillmann, I.F., Schaefer, H.G., Hermansson, K., Eriksson, B.I. The effect of BIBR 953 ZW, the active form of the oral direct thrombin inhibitor BIBR 1048, on the prolongation of aPTT and ECT in orthopedic patients: A population pharmacodynamic study. J Thromb Haemost 2003, 1(Suppl. 1): Abst P1917.
31. Eriksson, B.I., Dahl, O., Ahnfelt, L., Kalebo, P., Slangier, J., Nehmiz, G., Hermansson, K., Kohlbrenner, V. Dose escalating safety study of a new oral direct thrombin inhibitor, BIBR 1048, in patients undergoing total hip replacement (THR). Pathophysiol Haemost Thromb 2002, 32(Suppl. 2): Abst O124.
32. Garnett, C., Liesenfeld, K.H., Tillmann, C., Troconiz, I., Schaefer, H.G., Stangier, J., Lee, H. Clinical trial simulation of the dose-response relationship of a direct thrombin inhibitor, dabigatran etexilate, in hip replacement patients. 12th Meet Population Approach Group Eur (June 12-13, Verona) 2003, Abst 388.
33. Liesenfeld, K.H., Tillmann, I., Troconiz, I., Schaefer, H.G., Stangier, J. Population pharmacodynamic analysis of dabigatran, the active form of the new oral direct thrombin inhibitor dabigatran etexilate (BIBR 1048), on the prolongation of aPTT and ECT in orthopaedic patients. 12th Meet Population Approach Group Eur (June 12-13, Verona) 2003, Abst 387.
34. Liesenfeld, K.-H., Stangier, J., Garnett, C., Tillmann, C., Troconiz, I., Lee, H., Schaefer, H.G. PK/PD-modeling (PK/PD) and clinical trial simulation (CTS) of early clinical data of a new oral direct thrombin inhibitor (dabigatran etexilate). 14th Meet Population Approach Group Eur (June 16-17, Pamplona) 2005, Abst 787.
35. Stangier, J., Liesenfeld, K.-H., Tillmann, C., Troconiz, I., Schaefer, H.G. Population pharmacok/netics/-dynamics of dabigatran, the active form of the new oral direct thrombin inhibitor dabigatran etexilate (BIBR 1048) in patients undergoing hip replacement. 12th Meet Population Approach Group Eur (June 12-13, Verona) 2003, Abst 3852E
36. Tillmann, C., Troconiz, I.F., Stangier, J., Liesenfeld, K.H., Schaefer, H.G. Population pharmacokinetic analysis of the new oral thrombin inhibitor dabigatran etexilate (BIBR1048) in patients undergoing primary elective total hip replacement surgery. 12th Meet Population Approach Group Eur (June 12-13, Verona) 2003, Abst 386.
37. Stangier, J., Nehmiz, G., Liesenfeld, K.H., Holzschuh, I., Hermansson, K., Svaerd, R., Dahl, O.E., Ahnfelt, L., Eriksson, B.I. Pharmacokinetics of BIBR 953 ZW, the active form of the oral direct thrombin inhibitor BIBR 1048, in patients undergoing hip replacement. J Thromb Haemost 2003, 1(Suppl. 1): Abst P1916.
38. Gustafsson, D. Oral direct thrombin inhibitors in clinical development. J Intern Med 2003, 254(4): 322-34.
39. Kikelj, D. Peptidomimetic thrombin inhibitors. Pathophysiol Haemost Thromb 2003/2004, 33(5-6): 487-91.
40. Heit, J. A The potential role of direct thrombin inhibitors in the prevention and treatment of venous thromboembolism. Chest 2003, 124(3): 40S-8S.
41. Bates, S.M., Weitz, J.I. New anticoagulants: Beyond heparin, low-molecular-weight heparin and warfarin. Br J Pharmacol 2005, 144(8): 1017-28.