PHARMACOKINETIC AND PRECLINICAL STUDIES WITH RETEPLASE

Reteplase is a novel recombinant plasminogen activator consisting of t he kringle 2 and protease domains of t-PA. Due to its production in Es cherichia coli cells, reteplase is not glycosylated. As shown experime ntally, consequences of the structural changes are a virtual lack of f unctional fibrin binding and a lower affinity to endothelial cells and liver cells, resulting in a longer half-life. The longer half-life of reteplase and its ability to easily penetrate into a clot compared wi th t-PA have an impact on pharmacodynamic characteristics: they contri bute to the higher thrombolytic potency, allowing dose reduction, and enable i.v. bolus injection, which is associated with more rapid reper fusion than after administration of reference thrombolytic agents. The double bolus regimen of reteplase was experimentally shown to stabili ze coronary artery blood flow after successful reperfusion. At equieff ective doses, the degree of the systemic lytic state after reteplase i s comparable to that after t-PA.