<br>依立托兰四钠 (E5564) 治疗脓毒症：临床前和临床研究回顾。,Expert Opinion on Drug Metabolism & Toxicology

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依立托兰四钠 (E5564) 治疗脓毒症：临床前和临床研究回顾。
Expert Opinion on Drug Metabolism & Toxicology ( IF 3.9 ) Pub Date : 2011-02-17 , DOI: 10.1517/17425255.2011.558190
Amisha Barochia ₁ , Steven Solomon , Xizhong Cui , Charles Natanson , Peter Q Eichacker

Affiliation

引言脓毒症仍然是全世界死亡的主要原因。尽管进行了多年的广泛研究，但仍缺乏抑制脂多糖 (LPS) 促炎作用并在常规脓毒症治疗中添加时改善预后的有效药物。依立托兰四钠 (E5564) 是一种很有前途的脓毒症候选疗法，属于一类新型药物，通过阻断 Toll 样受体 4 来抑制 LPS 诱导的炎症。涵盖领域本综述重点关注在脓毒症中使用依立托兰四钠的基本原理以及其药代动力学、药效学、功效和安全性。讨论了 2010 年 8 月 MEDLINE/PubMed 文献检索中检索词“eritoran”和“E5564”的临床前和临床研究。专家意见依立托伦四钠的临床前体外和体内研究表明，它可以限制与 LPS 相关的过度炎症介质释放，并提高脓毒症模型的生存率。虽然早期临床结果令人鼓舞，但其治疗脓毒症患者的疗效和安全性目前仍在研究中。即使正在进行的招募患有严重脓毒症和死亡风险增加的患者的 III 期临床试验显示依立托伦有益，但问题仍然存在，需要进行验证性研究来确定其临床用途。

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Eritoran tetrasodium (E5564) treatment for sepsis: review of preclinical and clinical studies.

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.

更新日期：2019-11-01

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