In vitro studies demonstrate that Tenecteplase displays at least a 10-fold higher fibrin specificity and an 80-fold higher resistance to inhibition by plasminogen activator inhibitor (PAI-1) than native tPA. The increased fibrin specificity reduces the propensity for causing peripheral bleeding and ameliorates the risk of cerebral hemorrhage in a rabbit model of embolic stroke. Tenecteplase is cleared from the plasma in humans with an initial half-life of 20 to 24 min and a terminal plasma half-life of 90 to 130 min. The molecule displays an altered glycosylation pattern as compared with native tPA. It does not contain high-mannose oligosaccharides and therefore the hepatic mannose receptor, which plays an important role in native tPA removal, is unlikely to be involved in Tenecteplase elimination. Instead, the hepatic low-density receptor-related protein (LRP) as well as the hepatic asialoglycoprotein receptor may mediate removal.
A number of clinical studies have investigated the safety and efficacy of Tenecteplase [42-45]. ASSENT-2 was a major (n = 16,949) international randomized double-blind trial that compared Tenecteplase and native tPA (Activase). All patients also received aspirin and heparin. Rates of 30-day mortality (6.2% in both), intracranial hemorrhage (0.9% in both), and stroke (1.8 vs. 1.7%) revealed no significant differences between products.
The TIMI 10B study  was an open-label dose ranging randomized angiography study in which patients (n = 837) were treated with fixed doses of 30, 40, or 50 mg Tenecteplase or accelerated infusion with Activase. The results revealed that 40- or 50-mg doses produced similar results to Activase in terms of restoring patency.
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