Clinical development of PEGylated recombinant staphylokinase (PEG-Sak) for bolus thrombolytic treatment of patients with acute myocardial infarction.
The development of bolus thrombolytic agents, in conjunction with bolus anti-thrombotics (e.g. low molecular weight heparins), remains an ambitious but achievable goal of therapy for acute myocardial infarction-a disease which takes the lives of millions each year. This chapter summarizes the data accumulated over nearly a decade of investigation of recombinant staphylokinase (Sak) as a safe, cost-effective thrombolytic agent. The results of extensive animal investigations suggested this agent exhibited a uniquely fibrin-selective mechanism of action. Administration of various recombinant versions of the molecule to over 1000 patients on a global scale suggest this agent may be as effective as tissue-type plasminogen activator (rt-PA) in achieving prompt arterial recanalization of acutely occluded coronary arteries. The development of this protein as a single bolus agent is described in detail, and the results of recently completed international trials comparing this bolus agent to front-loaded rt-PA are summarized.
D000818:Animals; D002986:Clinical Trials as Topic; D005343:Fibrinolytic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006207:Half-Life; D006801:Humans; D008666:Metalloendopeptidases / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*
D005343:Fibrinolytic Agents; D011092:Polyethylene Glycols; D008666:Metalloendopeptidases; C461653:PEGylated staphylokinase SY161