Deposition and absorption of inhaled drugs

Main objectives of this thesis were to evaluate a gamma scintigraphic method used to quantify drug aerosol deposition in the lung, to investigate the influence of two aerosol inhalation parameters on the distribution of inhaled dry powder within the airways, to assess pulmonary absorption kinetics and bioavailability of an inhaled hydrophilic solute in relation to site of deposition, and to assess the influence of a surface active agent (sodium taurocholate, a bile salt) on the deposition and absorption of an inhaled hydrophilic solute. Repeated planar gamma scintigraphy was found to provide the same information on total pulmonary drug deposition as an independent method that involved assessments of urinary drug recovery after blockage of gastrointestinal drug absorption when all of the critical parts of the methodological procedures were accurately and meticulously executed. In this work, the inhalation flow used at dry powder aerosol inhalation did not appear to influence intrapulmonary deposition pattern or total pulmonary deposition. On the other hand, dose delivery late in the breath was observed to increase dry powder aerosol penetration into the lung as a consequence of the greater lung volume and, thus, larger airway dimensions that the aerosol particles encountered. The main pulmonary elimination pathway for the inhaled hydrophilic drug solute was found to be trans-epithelial absorption, whereas mucociliary clearance was less important. Independent of intrapulmonary aerosol deposition pattern, absorption of was rapid and extensive. Both rate and extent of absorption increased by the surface active agent