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Site of deposition and absorption of an inhaled hydrophilic solute

Bondesson, Eva LU ; Bengtsson, Thomas; Nilsson, Lars-Erik and Wollmer, Per LU (2007) In British Journal of Clinical Pharmacology 63(6). p.722-731
Abstract
Aims To characterize the absorption kinetics and bioavailability of an inhaled hydrophilic solute deposited at various sites within the airways. Methods Nine healthy nonsmokers received one intravenous, one oropharyngeal and two pulmonary doses of technetium-99 m-labelled diethylene triamine pentaacetic acid (Tc-99m-DTPA) in an open and crossover fashion. Pulmonary doses were administered as nebulized large and fine droplet-sized aerosols by Pari and UltraVent nebulizers at fairly rapid and slow inhalation flows, respectively. Plasma concentration-time profiles and 24 h urinary excretion of radioactivity were determined. One dose of Tc-99m-labelled Nanocoll, as a marker of mucociliary clearance (MCC), was also administered by Pari for... (More)
Aims To characterize the absorption kinetics and bioavailability of an inhaled hydrophilic solute deposited at various sites within the airways. Methods Nine healthy nonsmokers received one intravenous, one oropharyngeal and two pulmonary doses of technetium-99 m-labelled diethylene triamine pentaacetic acid (Tc-99m-DTPA) in an open and crossover fashion. Pulmonary doses were administered as nebulized large and fine droplet-sized aerosols by Pari and UltraVent nebulizers at fairly rapid and slow inhalation flows, respectively. Plasma concentration-time profiles and 24 h urinary excretion of radioactivity were determined. One dose of Tc-99m-labelled Nanocoll, as a marker of mucociliary clearance (MCC), was also administered by Pari for similar lung deposition as the Tc-99m-DTPA and followed by repeated chest gamma-imaging. Results Intrapulmonary deposition patterns of Tc-99m-DTPA differed significantly (the mean ratio of penetration index (Pari : UltraVent) was 76% with 95% CI 63%, 91%). However, no differences in rate or extent of Tc-99m-DTPA absorption were detected. Mean absorption time was 1.8 h (mean difference (Pari-UltraVent): -0.1 h with 95% CI -0.6 h, 0.3 h) and the bioavailability was 70% (mean ratio (Pari : UltraVent): 101% with 95% CI 90%, 115%). The pulmonary elimination half-life of Tc-99m-Nanocoll (8 h and 45 min) was significantly longer than that of Tc-99m-DTPA (less than 2 h). The oral bioavailability of Tc-99m-DTPA was estimated to be 3.1%. Conclusions The main elimination pathway of the inhaled hydrophilic solute Tc-99m-DTPA from the lungs is trans-epithelial absorption. Despite different intrapulmonary radioaerosol deposition patterns, as verified by gamma scintigraphy, no differences in Tc-99m-DTPA absorption kinetics or bioavailability were detected. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
pharmacokinetics, mucociliary clearance, lung deposition, aerosol, drug absorption, technetium-99 m
in
British Journal of Clinical Pharmacology
volume
63
issue
6
pages
722 - 731
publisher
John Wiley & Sons
external identifiers
  • wos:000246576800011
  • scopus:34248531775
ISSN
1365-2125
DOI
10.1111/j.1365-2125.2006.02835.x
language
English
LU publication?
yes
id
e1a72d4f-b036-419e-8f95-b154bfe2f403 (old id 659684)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17244190&dopt=Abstract
date added to LUP
2007-12-11 14:15:54
date last changed
2017-01-01 04:22:59
@article{e1a72d4f-b036-419e-8f95-b154bfe2f403,
  abstract     = {Aims To characterize the absorption kinetics and bioavailability of an inhaled hydrophilic solute deposited at various sites within the airways. Methods Nine healthy nonsmokers received one intravenous, one oropharyngeal and two pulmonary doses of technetium-99 m-labelled diethylene triamine pentaacetic acid (Tc-99m-DTPA) in an open and crossover fashion. Pulmonary doses were administered as nebulized large and fine droplet-sized aerosols by Pari and UltraVent nebulizers at fairly rapid and slow inhalation flows, respectively. Plasma concentration-time profiles and 24 h urinary excretion of radioactivity were determined. One dose of Tc-99m-labelled Nanocoll, as a marker of mucociliary clearance (MCC), was also administered by Pari for similar lung deposition as the Tc-99m-DTPA and followed by repeated chest gamma-imaging. Results Intrapulmonary deposition patterns of Tc-99m-DTPA differed significantly (the mean ratio of penetration index (Pari : UltraVent) was 76% with 95% CI 63%, 91%). However, no differences in rate or extent of Tc-99m-DTPA absorption were detected. Mean absorption time was 1.8 h (mean difference (Pari-UltraVent): -0.1 h with 95% CI -0.6 h, 0.3 h) and the bioavailability was 70% (mean ratio (Pari : UltraVent): 101% with 95% CI 90%, 115%). The pulmonary elimination half-life of Tc-99m-Nanocoll (8 h and 45 min) was significantly longer than that of Tc-99m-DTPA (less than 2 h). The oral bioavailability of Tc-99m-DTPA was estimated to be 3.1%. Conclusions The main elimination pathway of the inhaled hydrophilic solute Tc-99m-DTPA from the lungs is trans-epithelial absorption. Despite different intrapulmonary radioaerosol deposition patterns, as verified by gamma scintigraphy, no differences in Tc-99m-DTPA absorption kinetics or bioavailability were detected.},
  author       = {Bondesson, Eva and Bengtsson, Thomas and Nilsson, Lars-Erik and Wollmer, Per},
  issn         = {1365-2125},
  keyword      = {pharmacokinetics,mucociliary clearance,lung deposition,aerosol,drug absorption,technetium-99 m},
  language     = {eng},
  number       = {6},
  pages        = {722--731},
  publisher    = {John Wiley & Sons},
  series       = {British Journal of Clinical Pharmacology},
  title        = {Site of deposition and absorption of an inhaled hydrophilic solute},
  url          = {http://dx.doi.org/10.1111/j.1365-2125.2006.02835.x},
  volume       = {63},
  year         = {2007},
}