Deposition and absorption of inhaled drugs

Abstract

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.

• author: Bondesson, Eva
• supervisor: Per Wollmer
• opponent: Prof. Dolovich, Myrna, McMaster University, Hamilton,
• organization: Clinical Physiology and Nuclear Medicine, Malmö (research group)
• publishing date: 2006
• type: Thesis
• publication status: published
• subject: Cardiac and Cardiovascular Systems; Respiratory Medicine and Allergy
• keywords: tomografi, radiologi, Klinisk fysiologi, medical instrumentation, tomography, radiology, Clinical physics, technetium-99m, radionuclide imaging, radioactive aerosol, powder inhaler, pharmacokinetics, mucociliary clearance, lung deposition, gamma scintigraphy, inhalation, deposition modelling, drug absorption, absorption enhancer, aerosol, medicinsk instrumentering, Physiology, Fysiologi
• pages: 118 pages
• defense location: Diagnostiskt Centrum, Universitetssjukhuset MAS, ingång 44, plan 2, rum 2005-2007
• defense date: 2006-01-20 13:15:00
• ISBN: 91-85481-31-9
• language: English
• LU publication?: yes
• additional info: E Bondesson, L Asking, L Borgström, L-E Nilsson, E Trofast and P Wollmer. 2002. In vitro and in vivo aspects of quantifying intrapulmonary deposition of a dry powder radioaerosol. Int. J. Pharm., vol 232 pp 149-156.; E Bondesson, T Bengtsson, L Borgström, L-E Nilsson, K Norrgren, E Trofast and P Wollmer. 2003. Planar gamma scintigraphy - points to consider when quantifying pulmonary dry powder aerosol deposition. Int. J. Pharm., vol 251 pp 33-47.; E Bondesson, T Bengtsson, L Borgström, L-E Nilsson, K Norrgren, B Olsson, M Svensson and P Wollmer. 2005. Dose delivery late in the breath can increase dry powder aerosol penetration into the lungs. J. Aerosol Med., vol 18 pp 23-33.; E Bondesson, T Bengtsson, L-E Nilsson and P Wollmer. . Site of deposition and absorption of inhaled hydrophilic solutes. (submitted); E Bondesson, T Bengtsson, L-E Nilsson and P Wollmer. . Effects of sodium taurocholate on the absorption of inhaled 99mTc-DTPA. (submitted)
• id: 29fa501c-998e-4d71-bac9-f3a2aa49d52c (old id 546004)
• date added to LUP: 2016-04-04 10:11:12
• date last changed: 2018-11-21 20:57:18