Zeitlinger Markus, Müller Markus, Joukhadar Christian
Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, Medical University of Vienna, Austria.
AAPS J. 2005 Oct 22;7(3):E600-8. doi: 10.1208/aapsj070362.
In vivo measurement of concentrations of drugs and endogenous substances at the site of action has become a primary focus of research. In this context the minimal invasive microdialysis (MD) technique has been increasingly employed for the determination of pharmacokinetics in lung. Although lung MD is frequently employed to investigate various drugs and endogenous substances, the majority of lung MD studies were performed to determine the pharmacokinetic profile of antimicrobials that can be related to the importance of respiratory tract infections. For the lower respiratory tract various methods, such as surgical collection of whole lung tissue and bonchoalveolar lavage (BAL), are currently available for the determination of pharmacokinetics of antimicrobials. Head-to-head comparison of pharmacokinetics of antibiotics in lung revealed high differences between MD and conventional methods. MD might be regarded as a more advantageous approach because of its higher anatomical resolution and the ability to obtain dynamic time-vs-concentration profiles within one subject. However, due to ethical objections lung MD is limited to animals or patients undergoing elective thoracic surgery. From these studies it was speculated that the concentrations in healthy lung tissue may be predicted reasonably by the measurement of concentrations in skeletal muscle tissue. However, until now this was only demonstrated for beta-lactam antibiotics and needs to be confirmed for other classes of antimicrobials. In conclusion, the present review shows that MD is a promising method for the determination of antimicrobials in the lung, but might also be applicable for measuring a wide range of other drugs and for the investigation of metabolism in the lower respiratory tract.
在作用部位对药物和内源性物质浓度进行体内测量已成为研究的主要焦点。在此背景下,微创微透析(MD)技术越来越多地用于测定肺部的药代动力学。尽管肺部MD经常用于研究各种药物和内源性物质,但大多数肺部MD研究是为了确定抗菌药物的药代动力学特征,这可能与呼吸道感染的重要性有关。对于下呼吸道,目前有多种方法可用于测定抗菌药物的药代动力学,如手术采集全肺组织和支气管肺泡灌洗(BAL)。肺部抗生素药代动力学的直接比较显示,MD与传统方法之间存在很大差异。由于MD具有更高的解剖分辨率以及能够在一个受试者体内获得动态的时间-浓度曲线,因此它可能被认为是一种更具优势的方法。然而,由于伦理方面的反对,肺部MD仅限于动物或接受择期胸外科手术的患者。从这些研究推测,通过测量骨骼肌组织中的浓度可以合理预测健康肺组织中的浓度。然而,到目前为止,这仅在β-内酰胺类抗生素中得到证实,其他类别的抗菌药物需要进一步确认。总之,本综述表明,MD是一种用于测定肺部抗菌药物的有前景的方法,但也可能适用于测量多种其他药物以及研究下呼吸道的代谢。