TNK-tissue plasminogen activator in acute myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI) 10A dose-ranging trial

Circulation
C P CannonE Braunwald

Abstract

TNK-tissue plasminogen activator (TNK-TPA) is a genetically engineered variant of TPA, which in experimental models has a slower plasma clearance and greater fibrin specificity and is 80-fold more resistant to plasminogen activator inhibitor-1 than alteplase TPA. The thrombolysis in Myocardial Infarction (TIMI) 10A trial was a Phase 1, dose-ranging pilot trial designed to evaluate the pharmacokinetics, safety, and efficacy of TNK-TPA in patients with acute myocardial infarction. One hundred thirteen patients with acute ST-segment elevation myocardial infarction presenting within 12 hours and without contraindications to thrombolysis were enrolled and treated with a single bolus of TNK-TPA over 5 to 10 seconds with doses ranging from 5 to 50 mg. TNK-TPA demonstrated a plasma clearance of 151 +/- 55 mL/min and a half-life of 17 +/- 7 minutes. Comparable values for wild-type TPA are 572 +/- 132 mL/min and 3.5 +/- 1.4 minutes, respectively. Systemic fibrinogen and plasminogen levels fell by only 3% and 13%, respectively, at 1 hour after TNK-TPA administration. TIMI grade 3 flow at 90 minutes was achieved in 57% to 64% of patients at the 30- to 50-mg doses. Seven patients (6.2%) experienced a major hemorrhage, which occurred at a va...Continue Reading

References

Apr 1, 1992·Journal of the American College of Cardiology·P TanswellE Seifried
Apr 1, 1992·Journal of the American College of Cardiology·S R TorrB E Sobel
Apr 4, 1985·The New England Journal of Medicine·UNKNOWN TIMI Study Group
Apr 26, 1994·Proceedings of the National Academy of Sciences of the United States of America·B A KeytJ Ogez
Sep 2, 1993·The New England Journal of Medicine·UNKNOWN GUSTO investigators
Nov 25, 1993·The New England Journal of Medicine·E Braunwald
Aug 5, 1993·The New England Journal of Medicine·UNKNOWN European Myocardial Infarction Project Group
Mar 9, 1995·Journal of Interventional Cardiology·C P CannonE M Antman
Jan 1, 1994·Journal of Thrombosis and Thrombolysis·C P CannonE Braunwald

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Citations

Jul 21, 1998·Clinical Cardiology·C R Conti
Mar 20, 1999·Clinical Cardiology·A M Ross
Sep 18, 2001·Clinical Cardiology·C M Gibson, S J Marble
Jul 14, 2010·Journal of Thrombosis and Thrombolysis·Steven FishbaneSusan M Begelman
Feb 17, 2001·The American Journal of Cardiology·C M GibsonUNKNOWN Thrombolysis in Myocardial Infarction (TIMI) Study Group
Dec 24, 1997·Progress in Cardiovascular Diseases·A E Schussheim, V Fuster
Sep 25, 2001·Thrombosis Research·P Sinnaeve, F Van de Werf
Aug 25, 2001·Clinical Therapeutics·L Davydov, J W Cheng
Nov 5, 2002·Resuscitation·David CaldicottFelix Bochner
Jul 14, 2001·Critical Care Clinics·R Sundrani, L W Klein
Nov 1, 2001·Dimensions of Critical Care Nursing : DCCN·M J De Jong, W Sabadie-Garretson
Mar 31, 1999·The Journal of Cardiovascular Nursing·E S McErlean
Mar 26, 2009·European Journal of Emergency Medicine : Official Journal of the European Society for Emergency Medicine·Patrick GoldsteinJean Michel Juliard
Oct 20, 1998·Australian and New Zealand Journal of Medicine·P Aylward
Dec 7, 2007·Postgraduate Medical Journal·J B Jones, A Docherty
Mar 12, 2005·Journal of Endovascular Therapy : an Official Journal of the International Society of Endovascular Specialists·Kenneth Ouriel
May 14, 2009·Vascular Health and Risk Management·Giovanni MelandriAngelo Branzi
Sep 22, 2000·Sports Medicine·J M HagbergM D Brown
Nov 5, 2003·CNS Drugs·Geoffrey A DonnanStephen M Davis
Jan 13, 2015·TheScientificWorldJournal·Md Ramjan AliTasnim Fariha Noshin
Mar 16, 2007·Expert Opinion on Emerging Drugs·Paul A Lapchak, Dalia M Araujo
Nov 12, 2013·Indian Heart Journal·Jamshed DalalK A Sambasivam
Jul 10, 2013·Journal of Stroke and Cerebrovascular Diseases : the Official Journal of National Stroke Association·Jeffrey A SwitzerDavid C Hess
Feb 7, 2001·Chest·E M OhmanJ W Kennedy
May 5, 2007·Journal of Electrocardiology·Alejandro BarbagelataYochai Birnbaum
Dec 14, 2001·Journal of Vascular and Interventional Radiology : JVIR·D Y SzeM K Razavi
Nov 25, 2011·International Journal of Stroke : Official Journal of the International Stroke Society·Patrick Lyden
Oct 6, 2004·Pharmacotherapy·James P TsikourisGary E Meyerrose
Apr 11, 2009·Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions·John KanakakisMaria Anastasiou-Nana
Jul 11, 2012·The Journal of Pharmacy and Pharmacology·Martin Flemmig, Matthias F Melzig

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