Microdialysis in Lung Tissue: Monitoring of Exogenous and Endogenous Compounds

Feurstein, Thomas; Zeitlinger, Markus

doi:10.1002/9781118011294.ch7

Cited by 3 publications

(2 citation statements)

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“…The link between lung lining fluid and results in pharmacokinetic studies is complicated by the fact that usually plasma levels are predicted. Lung tissue levels are not easy to obtain in humans; the disadvantages of BAL measurements have already been mentioned, lung biopsies are not representative for the entire lung and represent only one time point and lung microdialysis is a highly invasive technique (Feuerstein and Zeitlinger, 2011 ). Lung microdialysis would be the ideal technique because continuous measurements of lung concentrations are possible.…”

Section: Effects Of Simulation Parameters On Deposition and Pharmacokmentioning

confidence: 99%

Measurements of Deposition, Lung Surface Area and Lung Fluid for Simulation of Inhaled Compounds

et al. 2016

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Modern strategies in drug development employ in silico techniques in the design of compounds as well as estimations of pharmacokinetics, pharmacodynamics and toxicity parameters. The quality of the results depends on software algorithm, data library and input data. Compared to simulations of absorption, distribution, metabolism, excretion, and toxicity of oral drug compounds, relatively few studies report predictions of pharmacokinetics and pharmacodynamics of inhaled substances. For calculation of the drug concentration at the absorption site, the pulmonary epithelium, physiological parameters such as lung surface and distribution volume (lung lining fluid) have to be known. These parameters can only be determined by invasive techniques and by postmortem studies. Very different values have been reported in the literature. This review addresses the state of software programs for simulation of orally inhaled substances and focuses on problems in the determination of particle deposition, lung surface and of lung lining fluid. The different surface areas for deposition and for drug absorption are difficult to include directly into the simulations. As drug levels are influenced by multiple parameters the role of single parameters in the simulations cannot be identified easily.

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Section: Effects Of Simulation Parameters On Deposition and Pharmacokmentioning

confidence: 99%

Measurements of Deposition, Lung Surface Area and Lung Fluid for Simulation of Inhaled Compounds

et al. 2016

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“…The first MD in lung tissue was performed in 1991 in rats; it was 10 years before a MD probe was inserted into a human lung. This might be explained by two major reasons: (1) ethical and safety concerns, and (2) alternative measurement techniques for lung [7]. For other organs like skin and muscle the human studies were developed in parallel with the animal experiments.…”

Section: Journal Of Clinical and Experimental Pharmacologymentioning

confidence: 99%

Microdialysis Techniques In Pharmacokinetic and Biomarker Studies Past, Present and Future Directions A Review

Erdő¹

2015

Clin Exp Pharmacol

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Microdialysis (MD) techniques were first applied in the early 1960s. The fields of their application comprised probe implantation into the central nervous system (CNS) at the beginning, and then expanded to almost every organ summarized in this article. After its early experimental applications MD became an important tool in the human pharmacokinetic/pharmacodynamic (PK/PD) studies as well. This monitoring technique is capable for investigation of local unbound concentrations of both endogenous and exogenous compounds in the interstitial fluid. The review shows examples for the role of MD in pharmacodynamic studies and for its use in tissue distribution and drug-transporter interaction studies. Determination of test substances in the dialysate samples needs sensitive bioanalytical methods. The main analytical techniques coupled with MD are summarized under the subtitle "Target molecules". New trend in the application of MD is the determination of large molecular entities in the extracellular fluid of target tissues. This approach greatly helps in the discovery of new pathophysiological pathways and identification of new therapeutic intervention strategies for several disorders. Finally, the article gives an overview on the complementary techniques (positron emission tomography, magnetic resonance spectroscopy and open flow microperfusion), and presents their advantages and limitations versus to in vivo MD. In summary, MD techniques have a wide variety of the fields of application. There are several new approaches using this methodology. The relatively low price and the importance of the information gained on the pharmacologically active form of the test articles at the site of interest guarantees a significant position of this technique in the preclinical and clinical research.

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Transport mechanisms at the pulmonary mucosa: implications for drug delivery

Nickel

Clerkin

Selo

et al. 2016

Expert Opinion on Drug Delivery

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Different tissue and cell populations of the lung have distinct transporter expression patterns. Whether these patterns are affected by disease, gender and smoking habits requires further clarification. Transporters have been found to have an impact on drug absorption processes, at least in vitro. Recent ex vivo experiments using isolated, perfused lung models, however, suggest that mainly efflux pumps have significant effects on absorption into the pulmonary circulation. Whether these rodent-based ex vivo models predict the human situation is basis for further research.

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Microdialysis in Lung Tissue: Monitoring of Exogenous and Endogenous Compounds

Cited by 3 publications

References 62 publications

Measurements of Deposition, Lung Surface Area and Lung Fluid for Simulation of Inhaled Compounds

Measurements of Deposition, Lung Surface Area and Lung Fluid for Simulation of Inhaled Compounds

Microdialysis Techniques In Pharmacokinetic and Biomarker Studies Past, Present and Future Directions A Review

Transport mechanisms at the pulmonary mucosa: implications for drug delivery

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