Drug absorption from inhalation aerosols administered by positive-pressure ventilation. II: Effect of disodium fluorescein aerosol particle size on fluorescein absorption kinetics in the beagle dog respiratory tract.

Solid, polydispersed disodium fluorescein aerosols (MMDae = 1.1, 3.5, and 4.4 micron) were administered under the same respiratory regime, direct to the respiratory tracts of two beagle dogs by positive-pressure ventilation. Subsequent to aerosol administration, plasma fluorescein concentrations were determined after sampling from an indwelling cannula. The amount absorbed as a function of time was estimated from these and additional data collected from intravenous control experiments in the same animals. Fluorescein absorption from the respiratory tract was apparently a first-order process, the rate increasing directly with the bioavailable dose. First-order rate constants differed but appeared unrelated to aerosol particle size, possibly reflecting similarities in their regional deposition in the canine lung. The average value for the absorption half-lives in the dogs were 19.3 and 12.2 min, showing that even lipophobic solutes such as the fluorescein dianion, are absorbed extremely rapidly via the lung. In one dog, the rate constant for fluorescein absorption after intratracheal instillation of a solution of the disodium salt was within the range of those following aerosol administration. Possible explanations are discussed.