Estimating in vivo airway surface liquid concentration in trials of inhaled antibiotics.

M A Hasan, C F Lange
{"title":"Estimating in vivo airway surface liquid concentration in trials of inhaled antibiotics.","authors":"M A Hasan,&nbsp;C F Lange","doi":"10.1089/jam.2007.0603","DOIUrl":null,"url":null,"abstract":"<p><p>Antibiotic drugs exhibit concentration dependence in their efficacy. Therefore, ensuring appropriate concentration of these drugs in the relevant body fluid is important for obtaining the desired therapeutic and physiological action. Until recently there had been no suitable method available to measure or estimate concentration of drugs in the human airways resulting from inhaled aerosols or to determine the amount of inhaled antibiotics required to ensure minimum inhibitory concentration of a drug in the airway surface liquid (ASL). In this paper a numerical method is used for estimating local concentration of inhaled pharmaceutical aerosols in different generations of the human tracheobronchial airways. The method utilizes a mathematical lung deposition model to estimate amounts of aerosols depositing in different lung generations, and a recent ASL model along with deposition results to assess the concentration of deposited drugs immediately following inhalation. Examples of concentration estimates for two case studies: one for the antibiotic tobramycin against Pseudomonas aeruginosa, and another for taurolidine against Burkholderia cepacia are presented. The aerosol characteristics, breathing pattern and properties of nebulized solutions were adopted from two recent clinical studies on efficacy of these drugs in cystic fibrosis (CF) patients and from other sources in the literature. While the clinically effective tobramycin showed a concentration higher than the required in vivo concentration, that for the ineffective taurolidine was found to be below the speculated required in vivo concentration. Results of this study thus show that the mathematical ASL model combined with the lung deposition model can be an effective tool for helping decide the optimum dosage of inhaled antibiotic drugs delivered during human clinical trials.</p>","PeriodicalId":14878,"journal":{"name":"Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine","volume":"20 3","pages":"282-93"},"PeriodicalIF":0.0000,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/jam.2007.0603","citationCount":"16","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1089/jam.2007.0603","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 16

Abstract

Antibiotic drugs exhibit concentration dependence in their efficacy. Therefore, ensuring appropriate concentration of these drugs in the relevant body fluid is important for obtaining the desired therapeutic and physiological action. Until recently there had been no suitable method available to measure or estimate concentration of drugs in the human airways resulting from inhaled aerosols or to determine the amount of inhaled antibiotics required to ensure minimum inhibitory concentration of a drug in the airway surface liquid (ASL). In this paper a numerical method is used for estimating local concentration of inhaled pharmaceutical aerosols in different generations of the human tracheobronchial airways. The method utilizes a mathematical lung deposition model to estimate amounts of aerosols depositing in different lung generations, and a recent ASL model along with deposition results to assess the concentration of deposited drugs immediately following inhalation. Examples of concentration estimates for two case studies: one for the antibiotic tobramycin against Pseudomonas aeruginosa, and another for taurolidine against Burkholderia cepacia are presented. The aerosol characteristics, breathing pattern and properties of nebulized solutions were adopted from two recent clinical studies on efficacy of these drugs in cystic fibrosis (CF) patients and from other sources in the literature. While the clinically effective tobramycin showed a concentration higher than the required in vivo concentration, that for the ineffective taurolidine was found to be below the speculated required in vivo concentration. Results of this study thus show that the mathematical ASL model combined with the lung deposition model can be an effective tool for helping decide the optimum dosage of inhaled antibiotic drugs delivered during human clinical trials.

估计吸入抗生素试验中气道表面液体浓度。
抗生素药物的疗效表现出浓度依赖性。因此,确保这些药物在相关体液中的适当浓度对于获得所需的治疗和生理作用是重要的。直到最近,还没有合适的方法来测量或估计吸入气溶胶引起的人体气道中的药物浓度,或确定吸入抗生素的量,以确保气道表面液体(ASL)中药物的最低抑制浓度。本文用数值方法估计了人体不同世代的气管-支气管中吸入的药物气溶胶的局部浓度。该方法利用数学肺沉积模型来估计不同肺代的气溶胶沉积量,并利用最近的ASL模型和沉积结果来评估吸入后立即沉积的药物浓度。两个案例研究的浓度估计的例子:一个针对铜绿假单胞菌的抗生素妥布霉素,另一个针对洋葱伯克霍尔德菌的牛磺酸定提出。雾化溶液的气溶胶特性、呼吸方式和特性采用了最近两项关于这些药物对囊性纤维化(CF)患者疗效的临床研究和文献中的其他来源。而临床上有效的妥布霉素的浓度高于体内所需浓度,无效的牛罗列丁的浓度低于推测的体内所需浓度。本研究结果表明,数学ASL模型与肺沉积模型相结合,可以作为一种有效的工具,帮助确定人体临床试验中吸入抗生素药物的最佳剂量。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信