Lung microdialysis--a powerful tool for the determination of exogenous and endogenous compounds in the lower respiratory tract (mini-review).
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.
Zeitlinger
Markus
M
Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, Medical University of Vienna, Austria. markus.zeitlinger@meduniwien.ac.at
Müller
Markus
M
Joukhadar
Christian
C
D000818:Animals; D000890:Anti-Infective Agents / Q000378:metabolism*; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D017551:Microdialysis / Q000295:instrumentation / Q000379:methods*; D012137:Respiratory System / Q000187:drug effects / Q000378:metabolism
D000890:Anti-Infective Agents