Microdialysis as a tool for drug quantification in the bronchioles of anaesthetized pigs
Lisa A H Rottbøll1, Christian Friis
1Department of Veterinary Disease Biology, Faculty of Health and Medical Science, Copenhagen University, Frederiksberg, Denmark.
Abstract:
Target site drug determinations are crucial for optimizing treatment of infectious diseases. There is limited knowledge of antibiotic drug penetration into the pulmonary epithelial lining fluid (PELF) and a lack of easily performed methods for continuous drug sampling hereof. The aim of this study was to develop a readily accessible microdialysis (MD) method for antibiotic drug quantification in PELF of pigs. The fluoroquinolone danofloxacin was administered to anaesthetized pigs allocated to three groups: intravenous injection, intravenous infusion and intramuscular injection. MD probes were guided through a tracheostomy into the distal bronchioles using an insertion tube. Intravenously administered inulin served as a marker of extracellular fluid contamination of PELF. Concentrations of free drug in MD fractions were compared to total and non-protein-bound drug concentrations in plasma. Rising and declining danofloxacin plasma concentrations were rapidly reflected in PELF, suggesting an efficient drug transport across the blood bronchial barrier. The AUC FREE DRUG PELF /AUC FREE DRUG PLASMA ratio was 1.8 (S.D. 0.4, 95% CL 1.4-2.3). Although the probes were placed without fiberscopic or other special equipment, the danofloxacin concentrations in PELF were consistent within the different administration groups. The described MD method for drug quantification in PELF is easily accessible and provides repeatable results. However, trace amount of inulin was detected in the MD fractions, suggesting a local tissue reaction induced by the MD membrane. The significance of this finding needs to be clarified in future studies.
Insights
This study introduces a simple microdialysis method to measure antibiotic drug levels in pulmonary epithelial lining fluid. The method shows efficient drug transport across the blood-bronchial barrier, aiding infectious disease treatment optimization.
Area of Science:
- Pharmacokinetics
- Drug delivery
- Respiratory medicine
Background:
- Optimizing infectious disease treatment requires understanding drug concentrations at the target site.
- Antibiotic penetration into pulmonary epithelial lining fluid (PELF) is poorly understood.
- A simple method for continuous drug sampling in PELF is lacking.
Purpose of the Study:
- To develop a readily accessible microdialysis (MD) method for antibiotic drug quantification in pig PELF.
- To assess danofloxacin drug penetration into PELF after different administration routes.
Main Methods:
- A microdialysis (MD) probe was inserted into the distal bronchioles of anesthetized pigs via tracheostomy.
- Danofloxacin was administered intravenously or intramuscularly.
- Inulin was used to assess extracellular fluid contamination of PELF samples.
Main Results:
- Danofloxacin concentrations in PELF rapidly mirrored plasma concentrations, indicating efficient blood-bronchial barrier transport.
- The AUC ratio of free drug in PELF to plasma was 1.8.
- The MD method provided consistent and repeatable danofloxacin quantification in PELF across administration groups.
Conclusions:
- The developed microdialysis method is easily accessible and provides repeatable results for antibiotic drug quantification in PELF.
- Efficient danofloxacin transport into PELF was demonstrated.
- A potential local tissue reaction due to the MD membrane warrants further investigation.
