title: Eritoran tetrasodium (E5564) treatment for sepsis: review of preclinical and clinical studies.
abstract: BACKGROUND
  Sepsis remains a leading cause of death worldwide. Despite years of extensive research, effective drugs that inhibit the pro-inflammatory effects of lipopolysaccharide (LPS) and improve outcome when added to conventional sepsis treatments are lacking. Eritoran tetrasodium (E5564) is a promising candidate therapy for sepsis belonging to a new class of such drugs which inhibit LPS-induced inflammation by blocking toll-like receptor 4.
  
  
  METHODS
  This review focuses on the rationale for the use of eritoran tetrasodium in sepsis as well as on its pharmacokinetics, pharmacodynamics, efficacy and safety. Preclinical and clinical studies from a MEDLINE/PubMed literature search in August 2010 with the search terms 'eritoran' and 'E5564' are discussed.
  
  
  CONCLUSIONS
  Preclinical in vitro and in vivo studies of eritoran tetrasodium indicate it can limit excessive inflammatory mediator release associated with LPS and improve survival in sepsis models. While early clinical results are promising, its efficacy and safety for treating patients with sepsis are currently under investigation. Even if the ongoing Phase III clinical trial enrolling patients with severe sepsis and increased risk of death shows benefit from eritoran, questions remain and confirmatory studies would be necessary to define its clinical usage.
authors.affiliation: Critical Care Medicine Department, Clinical Center, National Institutes of Health, Building 10, Room 2C145, Bethesda, MD 20892, USA. barochiaav@mail.nih.gov
authors.forename: Amisha
authors.initials: A
authors.lastname: Barochia
authors.forename: Steven
authors.initials: S
authors.lastname: Solomon
authors.forename: Xizhong
authors.initials: X
authors.lastname: Cui
authors.forename: Charles
authors.initials: C
authors.lastname: Natanson
authors.forename: Peter Q
authors.initials: PQ
authors.lastname: Eichacker
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002986:Clinical Trials as Topic; D004187:Disaccharides / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D018805:Sepsis / Q000188:drug therapy* / Q000401:mortality; D013403:Sugar Phosphates / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors
chemical_list: D000893:Anti-Inflammatory Agents; D004187:Disaccharides; D008070:Lipopolysaccharides; D013403:Sugar Phosphates; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; C512420:eritoran