一项I期临床试验，评估吸入乙醇在人体中的安全性、耐受性和药代动力学，将其作为呼吸道感染的一种潜在治疗方法。

A phase I clinical trial assessing the safety, tolerability, and pharmacokinetics of inhaled ethanol in humans as a potential treatment for respiratory tract infections.

作者信息

Hancock David G, Ditcham William, Ferguson Eleanor, Karpievitch Yuliya V, Stick Stephen M, Waterer Grant W, Clements Barry S

机构信息

Wal-yan Respiratory Research Centre, Telethon Kids Institute, University of Western Australia, Perth, WA, Australia.

UWA Medical School, University of Western Australia, Perth, WA, Australia.

出版信息

Front Med (Lausanne). 2024 Mar 5;11:1324686. doi: 10.3389/fmed.2024.1324686. eCollection 2024.

DOI:10.3389/fmed.2024.1324686

PMID:38504921

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10949138/

Abstract

BACKGROUND

Current treatments for respiratory infections are severely limited. Ethanol's unique properties including antimicrobial, immunomodulatory, and surfactant-like activity make it a promising candidate treatment for respiratory infections if it can be delivered safely to the airway by inhalation. Here, we explore the safety, tolerability, and pharmacokinetics of inhaled ethanol in a phase I clinical trial.

METHODS

The study was conducted as a single-centre, open-label clinical trial in 18 healthy adult volunteers, six with no significant medical comorbidities, four with stable asthma, four with stable cystic fibrosis, and four active smokers. A dose-escalating design was used, with participants receiving three dosing cycles of 40, 60%, and then 80% ethanol v/v in water, 2 h apart, in a single visit. Ethanol was nebulised using a standard jet nebuliser, delivered through a novel closed-circuit reservoir system, and inhaled nasally for 10 min, then orally for 30 min. Safety assessments included adverse events and vital sign monitoring, blood alcohol concentrations, clinical examination, spirometry, electrocardiogram, and blood tests.

RESULTS

No serious adverse events were recorded. The maximum blood alcohol concentration observed was 0.011% immediately following 80% ethanol dosing. Breath alcohol concentrations were high (median 0.26%) following dosing suggesting high tissue levels were achieved. Small transient increases in heart rate, blood pressure, and blood neutrophil levels were observed, with these normalising after dosing, with no other significant safety concerns. Of 18 participants, 15 completed all dosing cycles with three not completing all cycles due to tolerability. The closed-circuit reservoir system significantly reduced fugitive aerosol loss during dosing.

CONCLUSION

These data support the safety of inhaled ethanol at concentrations up to 80%, supporting its further investigation as a treatment for respiratory infections. identifier ACTRN12621000067875.

摘要

背景

目前针对呼吸道感染的治疗方法极为有限。乙醇具有独特的特性，包括抗菌、免疫调节和类似表面活性剂的活性，如果能够通过吸入安全地输送至气道，它将成为呼吸道感染治疗的一个有前景的候选药物。在此，我们在一项I期临床试验中探究吸入乙醇的安全性、耐受性和药代动力学。

方法

该研究作为一项单中心、开放标签的临床试验，纳入了18名健康成年志愿者，其中6名无明显合并症，4名患有稳定型哮喘，4名患有稳定型囊性纤维化，4名是现吸烟者。采用剂量递增设计，参与者在单次就诊时，每隔2小时接受三个给药周期，分别为40%、60%，然后是80%（体积比）乙醇水溶液。乙醇通过标准喷射雾化器雾化，通过一种新型闭路储液器系统输送，并经鼻吸入10分钟，然后经口吸入30分钟。安全性评估包括不良事件和生命体征监测、血液酒精浓度、临床检查、肺功能测定、心电图和血液检测。

结果

未记录到严重不良事件。在给予80%乙醇后即刻观察到的最高血液酒精浓度为0.011%。给药后呼出气酒精浓度较高（中位数为0.26%），表明达到了较高的组织水平。观察到心率、血压和血液中性粒细胞水平有短暂小幅升高，给药后这些指标恢复正常，无其他重大安全问题。18名参与者中，15名完成了所有给药周期，3名因耐受性问题未完成所有周期。闭路储液器系统显著减少了给药期间逃逸气溶胶的损失。