Pharmacokinetics and Pharmacodynamics of Lanoteplase (n-PA)

Thomas K. Nordt; Martin Moser; Benedikt Kohler; Wolfgang Kübler; Christoph Bode

doi:10.1055/s-0037-1615568

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1999; 82(S 01): 121-123
DOI: 10.1055/s-0037-1615568

Commentaries

Schattauer GmbH

Pharmacokinetics and Pharmacodynamics of Lanoteplase (n-PA)

Authors

Thomas K. Nordt

¹From the Abteilung Kardiologie, , Medizinische Klinik und Poliklinik, Universität Freiburg
Martin Moser

²Abteilung Kardiologie, Medizinische Klinik und Poliklinik, Universität Heidelberg, Germany
Benedikt Kohler

¹From the Abteilung Kardiologie, , Medizinische Klinik und Poliklinik, Universität Freiburg
Wolfgang Kübler

²Abteilung Kardiologie, Medizinische Klinik und Poliklinik, Universität Heidelberg, Germany
Christoph Bode

¹From the Abteilung Kardiologie, , Medizinische Klinik und Poliklinik, Universität Freiburg

Abstract

Summary

In acute myocardial infarction rapid, complete, and sustained reperfusion of the infarct-related coronary artery is the most important therapeutic principle. Lanoteplase or n-PA, a third-generation plasminogen activator consisting of a deletion and point mutant of tissue-type plasminogen activator (t-PA), is a promising agent to appraoch this therapeutic goal. The molecule exhibits an increased plasma half-life allowing single-bolus administration. In this article, after characterizing the n-PA molecule, the currently available pharmacokinetic and pharmacodynamic data including the results of the InTIME study are reviewed.

Key words

Myocardial infarction - reperfusion - thrombolysis - plasminogen - activator

Full Text

References

References
1 White HD, van de Werf FJJ. Thrombolysis for acute myocardial infarction. Circulation 1998; 97: 1632-46.
2 Fibrinolytic Therapy Trialists' (FTT) Collaborative Group. Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients. Lancet 1994; 343: 311-22.
3 Boersma E, Maas AC, Deckers JW, Simoons ML. Early thrombolytic treatment in acute myocardial infarction: reappraisal of the golden hour. Lancet 1996; 348: 771-5.
4 Newby LK, Rutsch WR, Califf RM, Simoons ML, Aylward PE, Armstrong PW, Woodlief LH, Lee KL, Topol EJ, van de Werf F. for the GUSTO-I Investigators Time from symptom onset to treatment and outcomes after thrombolytic therapy. J Am Coll Cardiol 1996; 27: 1646-55.
5 The GUSTO, Angiographic 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: 1615-22.
6 Ohman EM, Califf RM, Topol EJ, Candela R, Abbottsmith C, Ellis S, Sigmon KN, Kereiakes D, George B, Stack R, and the. TAMI Study Group Consequences of reocclusion after successful reperfusion therapy in acute myocardial infarction. Circulation 1990; 82: 781-91.
7 Smalling RW. Molecular biology of plasminogen activators: what are the clinical implications of drug design?. Am J Cardiol 1996; 78 (suppl 12A) 2-7.
8 Larsen GR, Timony GA, Horgan PG, Barone KM, Henson KS, Angus LB, Stoudemire JB. Protein engineering of novel plasminogen activators with increased thrombolytic potency in rabbits relative to activase. J Biol Chem 1991; 266: 8156-61.
9 den Heijer P, Vermeer F, Ambrosioni E, Sadowski Z, Lopez-Sendon JL, von Essen R, Beaufils P, Thadani U, Adgey J, Pierard L, Brinker J, Davies RF, Smalling RW, Wallentin L, Caspi A, Pangerl A, Trickett L, Hauck C, Henry D, Chew P. on behalf of the InTIME Investigators Evaluation of a weight-adjusted single-bolus plasminogen activator in patients with myocardial infarction. A double-blind, randomized angiographic trial of lanoteplase versus alteplase. Circulation 1998; 98: 2117-25.
10 Bode C, Smalling RW, Berg G, Burnett C, Lorch G, Kalbfleisch JM, Chernoff R, Christie LG, Feldman RL, Seals AA, Weaver WD. for the RAPID II Investigators Randomized comparison of coronary thrombolysis achieved with double-bolus reteplase (recombinant plasminogen activator) and front-loaded, accelerated alteplase (recombinant tissue plasminogen activator) in patients with acute myocardial infarction. Circulation 1996; 94: 891-8.
11 Liao WC, Beierle FA, Stouffer BC, Dockens RC, Abbud ZA, Tay LK, Knaus DM, Raymond RH, Chew PH, Kostis JB. Single bolus regimen of lanoteplase (nPA) in acute myocardial infarction: Pharmacokinetic evaluation from InTime-I Study. Circulation 1997; 96 (suppl.I) I 260-1 (abstract).
12 Kostis JB, Liao WC, Beierle FA, Ens GE, Tracy RP, Hauck CJ, Abbud ZA, Smith RA. Single bolus regimen of lanoteplase in acute myocardial infarction: hemostatic evaluation vs. tPA in the InTIME-I Study. Eur Heart J. 1998 19. 160 (abstract).
13 Nordt TK, Moser M, Kohler B, Ruef J, Peter K, Kubler W, Bode C. Augmented platelet aggregation as predictor of reocclusion after thrombolysis in acute myocardial infarction. Thromb Haemost 1998; 80: 881-6.
14 Ogata N, Ogawa H, Ogata Y, Numata Y, Morigami Y, Suefuji H, Soejima H, Sakomoto T, Yasue H. Comparison of thrombolytic therapies with mutant tPA (lanoteplase/SUN9216) and recombinant tPA (alteplase) for acute myocardial infarction. Japanese Circulation Journal 1998; 62: 801-6.