Lung microdialysis—A powerful tool for the determination of exogenous and endogenous compounds in the lower respiratory tract (mini-review)

Zeitlinger, Markus; Müller, Markus; Joukhadar, Christian

doi:10.1208/aapsj070362

Cited by 51 publications

(45 citation statements)

References 69 publications

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“…However, according to the literature (38), depending on the type of lung infection (pneumonia or endobronchial or other infections), the microorganism can be located in different compartments such as ISF, endothelial lining fluid, or alveolar or phagocytic cells, and different concentrations may be relevant for the effect. In the case of pneumonias, the free ISF concentrations determined in this study are relevant for bacterial killing.…”

Section: Discussionmentioning

confidence: 99%

Simultaneous Semimechanistic Population Analyses of Levofloxacin in Plasma, Lung, and Prostate To Describe the Influence of Efflux Transporters on Drug Distribution following Intravenous and Intratracheal Administration

Zimmermann

Laureano

Santos

et al. 2016

Antimicrob Agents Chemother

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Section: Discussionmentioning

confidence: 99%

Simultaneous Semimechanistic Population Analyses of Levofloxacin in Plasma, Lung, and Prostate To Describe the Influence of Efflux Transporters on Drug Distribution following Intravenous and Intratracheal Administration

Zimmermann

Laureano

Santos

et al. 2016

Antimicrob Agents Chemother

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“…An in vivo microdialysis perfusion technique was performed as previously described (28,29,37,43,45). Microdialysis is based on sampling of analytes from the extracellular space by a semipermeable membrane at the tip of a microdialysis probe.…”

Section: Methodsmentioning

confidence: 99%

Blood, Tissue, and Intracellular Concentrations of Erythromycin and Its Metabolite Anhydroerythromycin during and after Therapy

Krasniqi

Matzneller

Kinzig

et al. 2012

Antimicrob Agents Chemother

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For macrolides, clinical activity but also the development of bacterial resistance has been attributed to prolonged therapeutic and subtherapeutic concentrations. Although erythromycin is a long-established antimicrobial, concomitant determination of the pharmacokinetics of erythromycin and its metabolites in different compartments is limited. To better characterize the pharmacokinetics of erythromycin and its anhydrometabolite (anhydroerythromycin [AHE]) in different compartments during and after the end of treatment with 500 mg of erythromycin four times daily, concentration-time profiles were determined in plasma, interstitial space of muscle and subcutaneous adipose tissue, and white blood cells (WBCs) at days 1 and 3 of treatment and 2 and 7 days after end of therapy. In WBCs, concentrations of erythromycin exceeded those in plasma approximately 40-fold, while free concentrations in plasma and tissue were comparable. The observed delay of peak concentrations in tissue might be caused by fast initial cellular uptake. Two days after the end of treatment, subinhibitory concentrations were observed in plasma and interstitial space of both soft tissues, while 7 days after the end of treatment, erythromycin was not detectable in any compartment. This relatively short period of subinhibitory concentrations may be advantageous compared to other macrolides. The ratio of erythromycin over AHE on day 1 was highest in plasma (2.81 ؎ 3.45) and lowest in WBCs (0.27 ؎ 0.22). While the ratio remained constant between single dose and steady state, after the end of treatment the concentration of AHE declined more slowly than that of the parent compound, indicating the importance of the metabolite for the prolonged drug interaction of erythromycin. Macrolides account for 10 to 15% of the worldwide consumption of antibiotics (25,31). Although in many countries erythromycin has been replaced by newer relatives like azithromycin and clarithromycin, prescription of erythromycin still has a substantial place in less developed countries but also certain regions within Europe (15, 40). However, bacterial resistance against macrolides dramatically escalated in many countries during the last decades (14,23,35). Total consumption of antimicrobials on the one hand and the presence of long periods of exposure of bacterial populations to subinhibitory concentrations of antibiotics on the other hand are considered critical factors for selecting bacterial resistance (2, 3, 16).Erythromycin is known for its highly variable bioavailability after oral ingestion and its susceptibility toward degradation under acidic conditions. Although its half-life in plasma is short and the pharmacokinetic (PK) profile intraindividually heterogeneous, it is very well distributed throughout body tissues and accumulates in leukocytes (11). While clinical studies have shown the effectiveness of erythromycin in skin and soft tissue infections (33, 39), the in vivo penetration and the resulting free concentrations in interstitial space of soft tissues, i.e., the ...

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“…Microdialysis has also been applied as a means to quantify lung concentrations of antimicrobials in human subjects (83,85,94,142,146,147). However, a limitation of the technique in this setting is that pulmonary infections may be located in different compartments (e.g., alveoli, bronchioles, and intracellularly) (148). Consequently, it is important to choose a sampling technique that allows the determination of concentrations at or at least as close as possible to the infection site.…”

Section: In Vivo Studiesmentioning

confidence: 99%

Importance of Relating Efficacy Measures to Unbound Drug Concentrations for Anti-Infective Agents

2013

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SUMMARY For the optimization of dosing regimens of anti-infective agents, it is imperative to have a good understanding of pharmacokinetics (PK) and pharmacodynamics (PD). Whenever possible, drug efficacy needs to be related to unbound concentrations at the site of action. For anti-infective drugs, the infection site is typically located outside plasma, and a drug must diffuse through capillary membranes to reach its target. Disease- and drug-related factors can contribute to differential tissue distribution. As a result, the assumption that the plasma concentration of drugs represents a suitable surrogate of tissue concentrations may lead to erroneous conclusions. Quantifying drug exposure in tissues represents an opportunity to relate the pharmacologically active concentrations to an observed pharmacodynamic parameter, such as the MIC. Selection of an appropriate specimen to sample and the advantages and limitations of the available sampling techniques require careful consideration. Ultimately, the goal will be to assess the appropriateness of a drug and dosing regimen for a specific pathogen and infection.

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Lung microdialysis—A powerful tool for the determination of exogenous and endogenous compounds in the lower respiratory tract (mini-review)

Cited by 51 publications

References 69 publications

Simultaneous Semimechanistic Population Analyses of Levofloxacin in Plasma, Lung, and Prostate To Describe the Influence of Efflux Transporters on Drug Distribution following Intravenous and Intratracheal Administration

Simultaneous Semimechanistic Population Analyses of Levofloxacin in Plasma, Lung, and Prostate To Describe the Influence of Efflux Transporters on Drug Distribution following Intravenous and Intratracheal Administration

Blood, Tissue, and Intracellular Concentrations of Erythromycin and Its Metabolite Anhydroerythromycin during and after Therapy

Importance of Relating Efficacy Measures to Unbound Drug Concentrations for Anti-Infective Agents

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