Emergency and Critical Care Medicine, School of Medicine, Keio University, Tokyo, Japan.
Innate Immun. 2012 Dec;18(6):793-803. doi: 10.1177/1753425912441845. Epub 2012 Mar 29.
Eritoran, a synthetic analogue of lipid A, has been shown to bind to TLR4/MD-2 complex and thereby block the interaction of endotoxins with TLR4. We report here the results of a study conducted to assess the single-dose safety and tolerability, as well as the pharmacokinetics and pharmacodynamics, of eritoran infusion in Japanese and Caucasian healthy adult men. Sixty-four men (aged 20-45 years; body mass index 18-30 kg/m(2)) were randomized into four groups: 4-mg total dose (six Japanese and six Caucasian men); 12-mg total dose (12 Japanese and 12 Caucasian men); 28-mg total dose (six Japanese and six Caucasian men); and placebo (eight Japanese and eight Caucasian men). Eritoran in single doses up to 28 mg over 4 h was well tolerated, with no apparent ethnic differences noted. Plasma concentrations were slightly higher in Japanese versus Caucasian men; these differences were not significant after adjustment for differences in body mass (clearance: approximately 1.2 ml/h/kg; volume of distribution at steady state: approximately 0.07 l/kg). The ex vivo endotoxin inhibitory activity of eritoran was similar in Japanese and Caucasian men. The data do not indicate any need for clinical dose adjustment for possible ethnic-based differences in drug distribution or metabolism.
依利托林是脂多糖（lipid A）的一种合成类似物，它已被证实可以与 TLR4/MD-2 复合物结合，从而阻断内毒素与 TLR4 的相互作用。我们在此报告了一项研究的结果，该研究旨在评估依利托林输注在日本和高加索健康成年男性中的单次剂量安全性、耐受性、药代动力学和药效学。64 名男性（年龄 20-45 岁；体重指数 18-30kg/m²）被随机分为四组：4mg 总剂量（6 名日本人和 6 名高加索人）；12mg 总剂量（12 名日本人和 12 名高加索人）；28mg 总剂量（6 名日本人和 6 名高加索人）；和安慰剂（8 名日本人和 8 名高加索人）。依利托林在 4 小时内单次剂量高达 28mg 是可以耐受的，没有明显的种族差异。与高加索男性相比，日本男性的血浆浓度略高；但在调整体重差异后（清除率：约 1.2ml/h/kg；稳态时的分布容积：约 0.07l/kg），这些差异并不显著。依利托林对内毒素的体外抑制活性在日本和高加索男性中相似。数据表明，在药物分布或代谢方面，不需要根据种族差异进行临床剂量调整。
