TNK-tissue plasminogen activator in acute myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI) 10A dose-ranging trial
| Autor: | C M Gibson, Eugene Braunwald, Magdi Ghali, Nishit B. Modi, Carolyn H. McCabe, Rafael F. Sequeira, J Breed, Russel Tracy, Christopher P. Cannon, George R. McKendall, NL Fox, T W Love |
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| Rok vydání: | 1997 |
| Předmět: |
Adult
Male medicine.medical_specialty medicine.medical_treatment Myocardial Infarction Pilot Projects Fibrinogen Coronary Angiography Tissue plasminogen activator Fibrin Physiology (medical) Internal medicine medicine Humans Thrombolytic Therapy Myocardial infarction Aged biology Dose-Response Relationship Drug T-plasminogen activator business.industry Thrombolysis Middle Aged medicine.disease Blood Coagulation Factors Surgery Treatment Outcome Tissue Plasminogen Activator biology.protein Cardiology Female Cardiology and Cardiovascular Medicine business Plasminogen activator TIMI medicine.drug |
| Zdroj: | Circulation. 95(2) |
| ISSN: | 0009-7322 |
| Popis: | Background 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. Methods and Results 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 vascular access site in six patients. Conclusions TNK-TPA has a prolonged half-life so it can be administered as a single bolus. TNK-TPA appears to be very fibrin specific, and the initial patency and safety profiles are encouraging. Further study of this new thrombolytic agent is ongoing. |
| Databáze: | OpenAIRE |
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