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Eritoran tetrasodium (E5564) treatment for sepsis: review of preclinical and clinical studies
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INTRODUCTION: 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. AREAS COVERED: 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. EXPERT OPINION: 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.
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“Eritoran130 and resatorvid131 improved survival in animal models of sepsis, but did not reduce mortality in patients with severe sepsis132,133.”
From The gut microbiome and liver cancer: mechanisms and clinical translation (2017) · cites this paper as [130]
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Metadata
- Authors
- Barochia, A., Solomon, S., Cui, X., Natanson, C., & Eichacker, P. Q.
- Affiliations
- National Institutes of Health (US)
- Venue
- Expert Opinion on Drug Metabolism & Toxicology
- Publisher
- Informa Healthcare
- Published
- 2011-02-17
- Volume
- 7
- Issue
- 4
- Pages
- 479-494
- ISSN
- 1742-5255 (ISSN-L)
- 1744-7607
- PMC
- PMC3065179
- OpenAlex
- W2161681729
- Cited by
- 169
- References
- 66
- Citations by year
- 2026: 5 · 2025: 15 · 2024: 9 · 2023: 8 · 2022: 8 · 2021: 13 · 2020: 12 · 2019: 12 · 2018: 12 · 2017: 13 · 2016: 12 · 2015: 8 · 2014: 10 · 2013: 14 · 2012: 13
- FWCI
- 10.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Expert Opinion on Drug Metabolism & Toxicology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (Z99CL999999)
- Topics
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Sepsis Diagnosis and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
- Keywords
- sepsis, lipopolysaccharide, TLR4, anti-inflammatory therapy, pharmacokinetics, pharmacodynamics, drug safety, sepsis mortality, inflammatory mediator release
- MeSH terms
- Animals, Anti-Inflammatory Agents, Clinical Trials as Topic, Disaccharides, Dose-Response Relationship, Drug, Drug Evaluation, Preclinical, Humans, Lipopolysaccharides, Sugar Phosphates, Sepsis, Toll-Like Receptor 4, Drug-Related Side Effects and Adverse Reactions
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