| Tenecteplase, TNKase
TNKase was approved by the FDA as a fibrinolytic agent in 2000. This drug has a similar mechanism of action as alteplase (tPA). It is the latest thrombolytic agent approved for use in clinical practice. As of today, TNKase is currently indicated for the management of acute myocardial infarction.
Tenecteplase is produced by recombinant DNA technology using Chinese hamster ovary cells. This drug is a 527 amino acid glycoprotein, which sustained several modifications in amino acids molecules. These modifications consist of a substitution of threonine 103 with asparagine, asparagine 117 with glutamine, and a tetra-alanine substitution at amino acids 296-299 in the protease domain. This change permits TNKase to have a longer plasma half-life and more fibrin specificity. Tenecteplase has a half-life ranging initially from 20-24 minutes up to 130 minutes final clearance, most of it by liver metabolism.
Because of amino acids modifications, TNKase has the advantage for a single bolus administration and decreased bleeding side effects due to high fibrin specificity. The ASSENT-2 trial showed risk of major bleeding events to be less compared with alteplase 4.7% versus 5.9%. The incidence of hemorrhagic stroke was 0.9%, a little higher than alteplase, which showed 0.7% risk in the GUSTO trials.
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