Tetraphase Pharmaceuticals, Inc., Watertown, Massachusetts, USA.
Tetraphase Pharmaceuticals, Inc., Watertown, Massachusetts, USA
Antimicrob Agents Chemother. 2018 Oct 24;62(11). doi: 10.1128/AAC.01174-18. Print 2018 Nov.
Eravacycline is a novel, fully synthetic fluorocycline antibiotic with activity against aerobic and anaerobic Gram-positive and Gram-negative pathogens, including multidrug-resistant (MDR) bacteria. The pharmacokinetics (PK), urinary excretion, and safety/tolerability of intravenous (i.v.) eravacycline were evaluated in single- and multiple-ascending-dose studies. Healthy subjects received single i.v. doses of 0.1 to 3 mg/kg of body weight or 10 days of treatment with 0.5 or 1.5 mg/kg every 24 h (q24h) over 30 min, 1.5 mg/kg q24h over 60 min, or 1 mg/kg q12h over 60 min. After single doses, total exposure (the area under the plasma concentration-time curve [AUC]) and the maximum plasma concentrations () of eravacycline increased in an approximately dose-proportional manner. After multiple doses, steady state was achieved within 5 to 7 days. Accumulation ranged from approximately 7% to 38% with the q24h dosing regimens and was 45% with 1 mg/kg q12h. Eravacycline was generally well tolerated, with dose-related nausea, infusion site effects, and superficial phlebitis that were mild or moderate occurring. These results provide support for the 1-mg/kg q12h regimen used in clinical studies of eravacycline.
依拉环素是一种新型全合成氟环素类抗生素，具有抗需氧和厌氧革兰氏阳性和革兰氏阴性病原体的活性，包括多药耐药（MDR）细菌。在单次和多次递增剂量研究中评估了依拉环素的药代动力学（PK）、尿排泄和安全性/耐受性。健康受试者接受了单次静脉注射 0.1 至 3mg/kg 体重的剂量，或连续 10 天接受 0.5 或 1.5mg/kg 每 24 小时（q24h）一次，每次 30 分钟，1.5mg/kg 每 60 分钟一次，或 1mg/kg 每 12 小时一次，持续 60 分钟。单次给药后，依拉环素的总暴露量（血浆浓度-时间曲线下面积[AUC]）和最大血浆浓度（）呈近似剂量比例增加。多次给药后，在 5 至 7 天内达到稳态。q24h 给药方案的累积范围约为 7%至 38%，1mg/kg q12h 为 45%。依拉环素通常具有良好的耐受性，与剂量相关的恶心、输注部位效应和浅表性静脉炎的发生率为轻度或中度。这些结果为依拉环素临床研究中使用的 1mg/kg q12h 方案提供了支持。
