L Davydov1, J W Cheng. 1. Mount Sinai Medical Center, New York, NY 10029, USA.
Abstract
BACKGROUND: Certain shortcomings of the available thrombolytic agents have prompted the search for a more fibrin specific fibrinolytic agent with a longer half-life. Such properties would allow bolus administration, possibly leading to faster reperfusion of occluded arteries. OBJECTIVE: This article focuses on the new thrombolytic agent tenecteplase, reviewing its mechanism of action, pharmacokinetic characteristics, clinical efficacy, tolerability, and potential for drug interactions in the management of acute myocardial infarction. METHODS: English-language articles for inclusion in this review were identified through searches of MEDLINE, EMBASE, and International Pharmaceutical Abstracts from 1966 to April 2001. The search terms used included tenecteplase, myocardial infarction, TNK, and TNK-tPA. Abstracts from recent conferences and symposia were also consulted. RESULTS: Tenecteplase is a variant of the native tissue-type plasminogen activator (tPA) molecule that has 14-fold greater fibrin specificity than alteplase, a longer half-life, slower plasma clearance, and 80-fold greater resistance to inhibition by plasminogen activator inhibitor type 1. Its half-life of approximately 18 minutes allows single-bolus administration. In comparative clinical trials, tenecteplase was found to have equivalent efficacy to recombinant tPA (alteplase). The rate of intracranial hemorrhage with tenecteplase was similar to that with alteplase, and tenecteplase was associated with fewer noncerebral complications and less need for blood transfusions. CONCLUSIONS: Tenecteplase appears to be as effective and well tolerated as alteplase in the management of acute myocardial infarction and offers the convenience of single-bolus administration.
BACKGROUND: Certain shortcomings of the available thrombolytic agents have prompted the search for a more fibrin specific fibrinolytic agent with a longer half-life. Such properties would allow bolus administration, possibly leading to faster reperfusion of occluded arteries. OBJECTIVE: This article focuses on the new thrombolytic agent tenecteplase, reviewing its mechanism of action, pharmacokinetic characteristics, clinical efficacy, tolerability, and potential for drug interactions in the management of acute myocardial infarction. METHODS: English-language articles for inclusion in this review were identified through searches of MEDLINE, EMBASE, and International Pharmaceutical Abstracts from 1966 to April 2001. The search terms used included tenecteplase, myocardial infarction, TNK, and TNK-tPA. Abstracts from recent conferences and symposia were also consulted. RESULTS: Tenecteplase is a variant of the native tissue-type plasminogen activator (tPA) molecule that has 14-fold greater fibrin specificity than alteplase, a longer half-life, slower plasma clearance, and 80-fold greater resistance to inhibition by plasminogen activator inhibitor type 1. Its half-life of approximately 18 minutes allows single-bolus administration. In comparative clinical trials, tenecteplase was found to have equivalent efficacy to recombinant tPA (alteplase). The rate of intracranial hemorrhage with tenecteplase was similar to that with alteplase, and tenecteplase was associated with fewer noncerebral complications and less need for blood transfusions. CONCLUSIONS: Tenecteplase appears to be as effective and well tolerated as alteplase in the management of acute myocardial infarction and offers the convenience of single-bolus administration.
Authors: Sergei Zaitsev; Sergei Zaitzev; Dirk Spitzer; Juan-Carlos Murciano; Bi-Sen Ding; Samira Tliba; M Anna Kowalska; Khalil Bdeir; Alice Kuo; Victoria Stepanova; John P Atkinson; Mortimer Poncz; Douglas B Cines; Vladimir R Muzykantov Journal: J Pharmacol Exp Ther Date: 2009-12-01 Impact factor: 4.030