ArticleAntimicrobial agents and chemotherapy2004
Safety, pharmacokinetics, pharmacodynamics, and plasma lipoprotein distribution of eritoran (E5564) during continuous intravenous infusion into healthy volunteers.
Article in Antimicrobial agents and chemotherapy, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 73 citations in OpenAlex.
- Plasma protein distribution and its impact on pharmacokinetics of liposomal amphotericin B in paediatric patients with malignant diseases.European journal of clinical pharmacology · 2007Trial
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- First-in-human phase I clinical trial of a TLR4-binding DNA aptamer, ApTOLL: Safety and pharmacokinetics in healthy volunteers.Molecular therapy. Nucleic acids · 2022Article
- Lipoprotein Drug Delivery Vehicles for Cancer: Rationale and Reason.International journal of molecular sciences · 2019Review
- Inflammatory Response to Different Toxins in Experimental Sepsis Models.International journal of molecular sciences · 2019Review
- The Central Role of the Inflammatory Response in Understanding the Heterogeneity of Sepsis-3.BioMed research international · 2018Review
- Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-like Receptor Signaling.Journal of visualized experiments : JoVE · 2017Article
- Inhibition of Toll-Like Receptor Signaling as a Promising Therapy for Inflammatory Diseases: A Journey from Molecular to Nano Therapeutics.Frontiers in physiology · 2017Review
- Biology and Metabolism of Sepsis: Innate Immunity, Bioenergetics, and Autophagy.Surgical infections · 2016Review
- Toll-like Receptors in the Vascular System: Sensing the Dangers Within.Pharmacological reviews · 2016Review
- Toll-like receptor 4 (TLR4) antagonist eritoran tetrasodium attenuates liver ischemia and reperfusion injury through inhibition of high-mobility group box protein B1 (HMGB1) signaling.Molecular medicine (Cambridge, Mass.) · 2015Article
- Targeting toll-like receptors: promising therapeutic strategies for the management of sepsis-associated pathology and infectious diseases.Frontiers in immunology · 2013Review
- Toll-like receptors and opportunities for new sepsis therapeutics.Current infectious disease reports · 2012Article
- Eritoran tetrasodium (E5564) treatment for sepsis: review of preclinical and clinical studies.Expert opinion on drug metabolism & toxicology · 2011Review
- Neisseria meningitidis capsular polysaccharides induce inflammatory responses via TLR2 and TLR4-MD-2.Journal of leukocyte biology · 2011Article
- Toll Like Receptors Signaling Pathways as a Target for Therapeutic Interventions.Current signal transduction therapy · 2011Article
- Toll-like receptor 4 in CNS pathologies.Journal of neurochemistry · 2010Review
- Pathogen recognition receptors, cancer and inflammation in the gut.Current opinion in pharmacology · 2009Review
- Inhibition of corneal inflammation by the TLR4 antagonist Eritoran tetrasodium (E5564).Investigative ophthalmology & visual science · 2009Article
- Discovery and development of toll-like receptor 4 (TLR4) antagonists: a new paradigm for treating sepsis and other diseases.Pharmaceutical research · 2008Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Eritoran, a structural analogue of the lipid A portion of lipopolysaccharide (LPS), is an antagonist of LPS in animal and human endotoxemia models. Previous studies have shown that low doses (350 to 3,500 microg) of eritoran have demonstrated a long pharmacokinetic half-life but a short pharmacodynamic half-life. The present study describes the safety, pharmacokinetics and pharmacodynamics, and lipid distribution profile of eritoran during and after a 72-h intravenous infusion of 500, 2,000, or 3,500 microg/h into healthy volunteers. Except for the occurrence of phlebitis, eritoran administration over 72 h was safe and well tolerated. Eritoran demonstrated a slow plasma clearance (0.679 to 0.930 ml/h/kg of body weight), a small volume of distribution (45.6 to 49.8 ml/kg), and a relatively long half-life (50.4 to 62.7 h). In plasma, the majority (approximately 55%) of eritoran was bound to high-density lipoproteins. During infusion and for up to 72 h thereafter, ex vivo response of blood to 1- or 10-ng/ml LPS was inhibited by > or =85%, even when the lowest dose of eritoran (500 microg/h) was infused. Inhibition of response was dependent on eritoran dose and the concentration of LPS used as an agonist. Finally, in vitro analysis with purified lipoprotein and protein fractions from plasma obtained from healthy volunteers indicated that eritoran is inactivated by high-density but not low-density lipoproteins, very-low-density lipoproteins, or albumin. From these results, we conclude that up to 252 mg of eritoran can be safely infused into normal volunteers over 72 h and even though it associates extensively with high-density lipoproteins, antagonistic activity is maintained, even after infusion ceases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.