Document Detail


Site of deposition and absorption of an inhaled hydrophilic solute.
MedLine Citation:
PMID:  17244190     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 ((99m)Tc-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 (99m)Tc-labelled Nanocoll, as a marker of mucociliary clearance (MCC), was also administered by Pari for similar lung deposition as the (99m)Tc-DTPA and followed by repeated chest gamma-imaging.
RESULTS: Intrapulmonary deposition patterns of (99m)Tc-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 (99m)Tc-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 (99m)Tc-Nanocoll (8 h and 45 min) was significantly longer than that of (99m)Tc-DTPA (less than 2 h). The oral bioavailability of (99m)Tc-DTPA was estimated to be 3.1%.
CONCLUSIONS: The main elimination pathway of the inhaled hydrophilic solute (99m)Tc-DTPA from the lungs is trans-epithelial absorption. Despite different intrapulmonary radioaerosol deposition patterns, as verified by gamma scintigraphy, no differences in (99m)Tc-DTPA absorption kinetics or bioavailability were detected.
Authors:
Eva Bondesson; Thomas Bengtsson; Lars-Erik Nilsson; Per Wollmer
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-01-23
Journal Detail:
Title:  British journal of clinical pharmacology     Volume:  63     ISSN:  0306-5251     ISO Abbreviation:  Br J Clin Pharmacol     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-05-18     Completed Date:  2007-09-27     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  7503323     Medline TA:  Br J Clin Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  722-31     Citation Subset:  IM    
Affiliation:
AstraZeneca R and D Lund, SE-22187 Lund, Sweden. Eva.Bondesson@astrazeneca.com
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MeSH Terms
Descriptor/Qualifier:
Absorption
Administration, Inhalation
Adult
Aerosols / administration & dosage*
Chelating Agents / administration & dosage*,  pharmacokinetics
Cross-Over Studies
Humans
Lung / drug effects*
Male
Middle Aged
Mucociliary Clearance
Technetium Tc 99m Pentetate / administration & dosage*,  pharmacokinetics
Tomography, X-Ray Computed / methods
Chemical
Reg. No./Substance:
0/Aerosols; 0/Chelating Agents; 65454-61-7/Technetium Tc 99m Pentetate
Comments/Corrections

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