The preclinical and clinical pharmacology of Novastan (argatroban): A small-molecule, direct thrombin inhibitor

Clinical and Applied Thrombosis/Hemostasis

Volumn 3, Issue 1, 1997, Pages 1-15

  Schwarz Jr , Richard P ^a   Becker, Jean Claude P ^a   Brooks, R Lynn ^a   Hursting, Marcie J ^a   Joffrion, James L ^a   Knappenberger, Gary D ^a   Kogan, Timothy P ^a   Kogan, Patricia W ^a   McKinney, Anthony A ^a  

^a TEXAS BIOTECHNOLOGY CORPORATION   (United States)

Author keywords

Molecular properties; Novastan (argatroban); Pharmacology; Thrombin inhibitor

Indexed keywords

ARGATROBAN; HEPARIN; HEPARINOID; THROMBIN; THROMBIN INHIBITOR; WARFARIN;

ANTICOAGULATION; BLEEDING; BLOOD CLOT LYSIS; CLINICAL TRIAL; DRUG INDICATION; DRUG MECHANISM; DRUG METABOLISM; DRUG SAFETY; DRUG SELECTIVITY; HEART INFARCTION; HEART MUSCLE ISCHEMIA; HEMOSTASIS; HUMAN; KIDNEY FAILURE; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; REVIEW; THROMBOCYTOPENIA; VEIN THROMBOSIS;

EID: 13144265792     PISSN: 10760296     EISSN: None     Source Type: Journal    
DOI: 10.1177/107602969700300101     Document Type: Review

References (73)

1. Théroux P, Lidon R-M. Anticoagulants and their use in acute ischemic syndromes. In: Topol EJ, ed. A textbook of interventional cardiology. Philadelphia: W. B. Saunders, 1994:23.
2. Lefkovits J, Topol EJ. Direct thrombin inhibitors in cardiovascular medicine. Circulation 1994;90:1522.
3. Hirsh J. Heparin. N Engl J Med 1991;324:1565.
4. Rosenberg RD. The heparin-antithrombin system: a natural anticoagulant mechanism. In: Colman RW, Hirsch J, Marder VJ, et al., eds. Hemostasis and thrombosis: principles and clinical practice, 2nd ed. Philadelphia: J. B. Lipincott, 1987:1373.
5. Hirsh J, Dalen JE, Deykin D, et al. Oral anticoagulation: mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest 1992;102:312S.
6. Glazier RL, Crowell EB. Randomized prospective trial of continuous vs. intermittent heparin therapy. JAMA 1976; 236:1365.
7. Salzman EW, Deykin K, Shapiro RM, et al. Management of heparin therapy. N Engl J Med 1975;292:1046.
8. Marcianek E, Gockerman JP. Heparin-induced decrease in circulating antithrombin-III Lancet 1977;2:581.
9. Weitz JI, Huboda M, Massel D, et al. Clot-bound thrombin protected from inhibition by heparin-antithrombin III but is susceptible to inactivation by antithrombin III - independent inhibitors. J Clin Invest 1990;86:385.
10. Hogg PJ, Jackson CM. Fibrin monomer protects thrombin from inactivation by heparin-antithrombin III: implications for heparin efficacy. Proc Natl Acad Sci USA 1989;86:3619.
11. Teitel JM, Rosenberg RD. Protection of factor Xa from neutralization by the heparin-antithrombin complex. J Clin Invest 1983;71:1383.
12. Loscalzo J, Melnick B, Handin RI. The interaction of platelet factor 4 and glycosaminoglycans. Arch Biochem Biophys 1985;240:446.
13. Greinacher A. Antigen generation in heparin-associated thrombocytopenia: the nonimmunologic type and the immunologic type are closely linked in their pathogenests. Semin Thromb Hemost 1995;21:106.
14. Bell WR, Tomasulo PA, Alving BM, et al. Thrombocytopenia occurring during the administration of heparin: a prospective study in 52 patients. Ann Intern Med 1976;85:155.
15. Visentin GP, Ford SE, Scott JP, et al. Antibodies from patients with heparin-induced thrombocytopenia/thrombosis are specific for platelet factor a completed with heparin or bound to endothelial cells. J Clin Invest 1994;93:81.
16. Kelton JG, Sheridan D, Brain M, et al. Clinical usefulness of testing for a heparin-dependent platelet aggregating factor in patients with suspected heparin-associated thrombocytopenia. J Lab Clin Med 1984;103:606.
17. Weissman RE, Tobin RW. Arterial embolism occurring during systemic heparin therapy. Arch Surg 1958;76:219.
18. Wallis DE, Lewis BE, Pifarré R, et al. Active surveillance for heparin-induced thrombocytopenia and thromboembolism. Am Coll Chest Phys 1994;Oct. 30.
19. Magnani HN. Heparin-induced thrombocytopenia (HIT): an overview of 230 patients treated with Orgaran (Org 10172). Thromb Haemostas 1993;70:554.
20. Hirsh J, Levine MN. Low molecular weight heparin. Blood 1992;79:1.
21. Bara L, Billaud E, Gramond G, et al. Comparative pharmacokinetics of low molecular weight (PK 10169) and unfractionated heparin after intravenous and subcutaneous administration. Thromb Res 1985;39:631.
22. Handeland GF, Abidgaard GF, Holm U, et al. Doseadjusted heparin treatment of deep vein thrombosis: a comparison of unfractionated and low molecular weight heparin. Eur J Clin Pharmacol 1990;39:107.
23. Beguin S, Lindhout T, Hemker HC. The mode of action of heparin in plasma. Thromb Haemostas 1989;60:457.
24. Aster R. Heparin-induced thrombocytopenia and thrombosis. N Engl J Med 1995;332:1374.
25. Callas D, Fareed J. Comparative pharmacology of site directed antithrombin agents. Implication in drug development. Thromb Haemostas 1995;74:473.
26. Dodt J, Müller H-P, Seemüller U, et al. The complete amino acid sequence of hirudin, a thrombin specific inhibitor. FEBS Lett 1984;165:180.
27. Bush LR. Argatroban, a selective, potent thrombin inhibitor. Card Drug Rev 1991;9:247.
28. Stone SR, Betz A, Parry MAA, et al. Molecular basis for the inhibition of thrombin by hirudin. In: Claeson G, et al., ed. The design of synthetic inhibitors of thrombin. New York: Plenum Press, 1993:35.
29. Braun PJ, Dennis S, Hofsteenge J, et al. Use of site-directed mutagenesis to investigate the basis for the specificity of hirudin. Biochemistry 1988;27:6517.
30. Hijikata A, Okamoto S. A strategy for a rational approach to designing synthetic selective inhibitors. Semin Thromb Hemost 1992;18:135.
31. Jackson CM. Mechanisms of prothrombin activation. In: Colman RW, Hirsh J, Marder VJ, et al., eds. Hemostasis and thrombosis, 2nd ed. Philadelphia: J. B. Lipincott, 1987:1373.
32. Naski MC, Shafer JA. A kinetic model for the a-thrombincatalyzed conversion of plasma levels of fibrinogen to fibrin in the presence of antithrombin III. J Biol Chem 1991;266: 13003.
33. Lawson JH, Kalafatis M, Stram S, et al. A model for the tissue factor pathway to thrombin. J Biol Chem 1994;269: 23357.
34. Jones KC, et al. A model for the tissue factor pathway to thrombin. J Biol Chem 1994;269:23367.
35. Berry CN, Giradot C, Lecoffre C, et al. Effects of the synthetic thrombin inhibitor argatroban on fibrin- or clotincorporated thrombin: comparison with heparin and recombinant hirudin. Thromb Haemostas 1994;72:381.
36. Gast A, Tschopp TB, Schmid G, et al. Inhibition of clotbound and free (fluid-phase thrombin) by a novel synthetic thrombin inhibitor (Ro 46-6240), recombinant hirudin and heparin in human plasma. Blood Coag Fibrin 1994;5:879.
37. Mirshahi M, Soria J, Soria C, et al. Evaluation of the inhibition by heparin and hirudin of coagulation activation during r-tPA-induced thrombolysis. Blood 1989;74:1025.
38. Rawson TE, VanGorp KA, Yang J, et al. Separation of 21-(R)- and 21-(5)-argatroban: solubility and activity of the individual diastereoisomers. J Pharm Sci 1993;82:672.
39. Green D, Ts'ao C, Reynolds N, et al. In vitro studies of a new synthetic thrombin inhibitor. Thromb Res 1985;37:145.
40. Tamao Y, Yamamoto T, Kikumoto R, et al. Effect of a selective thrombin inhibitor MCI-9038 on fibrinolysis in vitro and in vivo. Thromb Haemostas 1986;56:28.
41. Berry CH, Girard D, Lochot S, et al. Antithrombotic actions of argatroban in rat models of venous, "mixed" and arterial thrombosis, and its effects on the tail transection bleeding time. Br J Pharmacol 1994;113:1209.
42. Winn MJ, Jain K, Ku DD. Argatroban and inhibition of the vasomotor actions of thrombin. J Cardiovasc Pharmacol 1993;22:754.
43. Kumada T, Abiko Y. Comparative study on heparin and a synthetic thrombin inhibitor no. 805 (MD-805) in experimental antithrombin deficient animals. Thromb Res 1981;24:285.
44. Nishiyama H, Umemura K, Saniabadi AR, et al. Enhancement of thrombolytic efficacy of tissue-type plasminogen activator by adjuvants in the guinea pig thrombosis model. Eur J Pharmacol 1994;264:191.
45. Mellott MJ, Connelly TM, York SJ, et al. Prevention of reocclusion by MCI-9038, a thrombin inhibitor, following t-PA induced thrombolysis in a canine model of femoreal arterial thrombosis. Thromb Haemostas 1990;64:526.
46. Jang, I-K, Gold HK, Leinbach RC, et al. In vivo thrombin inhibition enhances and sustains arterial recanalization with recombinant tissue plasminogen activator. Circ Res 1990;67: 1552.
47. 2 in reocclusion following coronary thrombolysis with tissue plasminogen activator. Proc Natl Acad Sci USA 1989;86:7585.
48. 2 modulate the response to tissue type plasminogen activator in vivo. Circ Res 1989;65:83.
49. Yasuda T, Gold HK, Yaoita H, et al. Comparative effects of aspirin, a synthetic thrombin inhibitor and a monoclonal antiplatelet glycoprotein IIb/IIIa antibody on coronary artery reperfusion, reocclusion and bleeding with recombinant tissue type plasminogen activator in a canine preparation. J Am Coll Cardiol 1990;16:714.
50. Eidt JF, Allison P, Noble S, et al. Thrombin is an important mediator of platelet aggregation in stenosed canine coronary arteries with endothelial injury. J Clin Invest 1989;84:18.
51. Iida S, Komatsu T, Hirano T, et al. Pharmacokinetic studies of argipidine (MD-805) in dogs and rabbits. Blood or plasma level profile, metabolism, excretion and accumulation after single or consecutive intravenous administration of argipidine. Oyo Yakuri 1986;32:1117.
52. Callas DD, Hoppensteadt D, Fareed J, et al. Comparative studies on the anticoagulant and protease generation inhibitory actions of newly developed site-directed thrombin inhibitory drugs. Semin Thromb Hemost 1995;21:177.
53. Kaiser B, Fareed J, Hoppensteadt D, et al. Influence of recombinant hirudin and unfractionated heparin on thrombin and factor Xa generation in extrinsic and intrinsic activated systems. Thromb Res 1992;65:157.
54. Kaiser B, Callas D, Hoppensteadt D, et al. Comparative studies on the inhibitory spectrum of recombinant hirudin, DuP 714 and heparin on the generation of thrombin and factor Xa generation in biochemically defined systems. Thromb Res 1994;73:327.
55. Izawa O, Katsuki M, Komatsu T, et al. Pharmacokinetics studies of argatroban (MD-805) in human concentrations of argatroban and its metabolites in plasma, urine and feces during and after drip intravenous infusion. Jpn Pharm Ther 1986;14:251.
56. Topol EJ. Thrombolytic intervention. In: Topol EJ, ed. A textbook of interventional cardiology. Philadelphia: W. B. Saunders, 1994:68.
57. The GUSTO Investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med 1993;329:673.
58. The GUSTO Angiographie Investigators. The effects of tissue plasminogen activator, streptokinase, or both on coronary-artery patency, ventricular function, and survival after acute myocardial infarction. N Engl J Med 1993;329:1615.
59. Becker RC. Improving the efficacy and stability of coronary reperfusion following thrombolysis: exploring the thrombin hypothesis. J Thromb Thrombolysis 1995;1:133.
60. Cannon CP, McCabe CH, Henry TD, et al. A pilot trial of recombinant desulfatohirudin compared with heparin in conjunction with tissue-type plasminogen activator and aspirin for acute myocardial infarction: results of the thrombolysis and myocardial infarction (TIMI) 5 trial. J Am Coll Cardiol 1994;23:993.
61. Lee LV, for the TIMI 6 Investigators. Initial experience with hirudin and streptokinase in acute myocardial infarction: results of the thrombolysis in myocardial infarction (TIMI) 6 trial. Am J Cardiol 1995;75:7.
62. Antman EM, for the TIMI 9A Investigators. Hirudin in acute myocardial infarction: safety report from the thrombolysis and thrombin inhibition in myocardial infarction (TIMI) 9A trial. Circulation 1994;90:1624.
63. GUSTO IIa Investigators. Randomized trial of intravenous heparin versus recombinant hirudin for acute coronary syndromes. Circulation 1994;90:1631.
64. Neuhaus K-L, Essen R, Tebbe U, et al. Safety observations from the pilot phase of the randomized r-hirudin for improvement of thrombolysis (HIT-III) study: a study of the Arbeitsgemeinschaft Leitender Kardiologischer Krankenhausärzte (ALKK). Circulation 1994;90:1638.
65. Sobel BE. Intracranial bleeding, fibrinolysis, and anticoagulation: causal connections and clinical implications. Circulation 1994;90:2147.
66. Théroux P, Perez-Villa F, Waters D, et al. Randomized double-blind comparison of two doses of hirulog with heparin as adjunctive therapy to streptokinase to promote early patency of the infarct-related artery in acute myocardial infarction. Circulation 1994;91:2132.
67. Gold HK, Torres FW, Garabedian HD, et al. Evidence for a rebound coagulation phenomenon after cessation of a 4-hour infusion of a specific thrombin inhibitor in patients with unstable angina pectoris. J Am Coll Cardiol 1993;21:1039.
68. Théroux P, Waters D, Lam J, et al. Reactivation of unstable angina following discontinuation of heparin. N Engl J Med 1992;327:141.
69. Willerson JT, Casscells W. Thrombin inhibitors in unstable angina: rebound or continuation of angina after argatroban withdrawal? J Am Coll Cardiol 1993;21:1048.
70. Zoldhelyi P, Bichler J, Owen WG, et al. Persistent thrombin generation in humans during specific thrombin inhibition with hirudin. Circulation 1994;90:2671.
71. Becker RC, Bovill EG, Corrao JM, et al. Dynamic nature of thrombin generation, fibrin formation, and platelet activation in unstable angina and non-Q-wave myocardial infarction. J Thromb Thrombolysis 1995;2:57.
72. Demers C, Ginsberg JS, Brill-Edwards P, et al. Rapid anticoagulation using ancrod for heparin-induced thrombocytopenia. Blood 1991;78:2194.
73. Lewis BE, Leya FS, Wallis D, et al. Failure of ancrod in the treatment of heparin-induced arterial thrombosis. Can J Cardiol 1994;10:559.