A novel dosing method for drug administration to the airways of the isolated perfused rat lung

A novel method is described for the reproducible administration of known liquid quantities to the peripheral airways of the isolated perfused rat lung. The basis of the technique was to use a 25-microL metered dose of fluorocarbon propellant to expel liquid (as a coarse spray) from an intratracheal dosing cartridge into the airways, while simultaneously inflating the lungs with a fixed volume of gas. The methodology is illustrated by administration of 100-microL volumes of aqueous disodium fluorescein solutions to a series of lung preparations. The reproducibility and regional distribution of dosing were determined by dissection, homogenization, and fluorimetric assay. Even though the dye was distributed nonuniformly between the lung lobes, in a series of preparations, 65.9 +/- 4.8% of the recovered dose was still deposited in the lung periphery, the site from which absorption is believed to occur. The method will enable the study of airway-to-perfusate transfer kinetics for compounds administered in a variety of different liquid formulations.