Possible Extraction of Drugs from Lung Tissue During Broncho-alveolar Lavage Suggest Uncertainty in the Procedure's Utility for Quantitative Assessment of Airway Drug Exposure

• Published in: Journal of pharmaceutical sciences 2022-03, Vol.111 (3), p.852-858
• Main Authors: Bäckström, E., Erngren, T., Fihn, B.-M., Sadiq, M.W., Lindberg, W., Fridén, M., Grime, K.
• Format: Article
• Language: English
• Subjects: Bronchoalveolar Lavage Fluid; Distribution; Lung; Pharmacokinetics; Propranolol; Protein binding; Pulmonary drug delivery; Therapeutic Irrigation; Tissue partition; Uncertainty
• ISSN: 0022-3549; 1520-6017; 1520-6017
• DOI: 10.1016/j.xphs.2021.12.004

Following inhaled dosing, broncho-alveolar lavage (BAL) is often used for sampling epithelial lining fluid (ELF) to determine drug concentration in the lungs. This study aimed to explore the technique's suitability. Urea is typically used to estimate the dilution factor between the BAL fluid and physiological ELF, since it readily permeates through all fluids in the body. As representatives of permeable small molecule drugs with high, medium and low tissue distribution properties, propranolol, diazepam, indomethacin and AZD4721 were infused intravenously to steady state to ensure equal unbound drug concentrations throughout the body. The results showed that propranolol had higher unbound concentrations in the ELF compared to the plasma whilst this was not the case for the other compounds. Experiments with different BAL volumes and repeated lavaging indicated that the amount of drug extracted is very sensitive to experimental procedure. In addition, the results show that the unbound concentrations in ELF compared to plasma differs dependent on molecule class and tissue distribution properties. Overall data suggests that lavaging can remove drug from lung tissue in addition to ELF and highlights significant uncertainty in the robustness of the procedure for determining ELF drug concentrations.