Clinical development of PEGylated recombinant staphylokinase (PEG-Sak) for bolus thrombolytic treatment of patients with acute myocardial infarction.

Abstract

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.

• Authors: Randall W Moreadith, Désiré Collen
• Journal: Advanced drug delivery reviews (Adv Drug Deliv Rev) Vol. 55 Issue 10 Pg. 1337-45 (Sep 26 2003) ISSN: 0169-409X [Print] Netherlands
• PMID: 14499711 (Publication Type: Journal Article, Review)

Chemical References

• Fibrinolytic Agents
• Polyethylene Glycols
• Metalloendopeptidases
• PEGylated staphylokinase SY161

Topics

• Animals
• Clinical Trials as Topic
• Fibrinolytic Agents (pharmacokinetics, therapeutic use)
• Half-Life
• Humans
• Metalloendopeptidases (chemistry, pharmacokinetics, therapeutic use)
• Middle Aged
• Myocardial Infarction (drug therapy)
• Polyethylene Glycols (chemistry, pharmacokinetics, therapeutic use)