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Site of deposition and absorption of an inhaled hydrophilic solute.

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 ((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.

journal_name

Br J Clin Pharmacol

journal_title

British journal of clinical pharmacology

authors

Bondesson E,Bengtsson T,Nilsson LE,Wollmer P

doi

10.1111/j.1365-2125.2006.02835.x

subject

Has Abstract

pub_date

2007-06-01 00:00:00

pages

722-31

issue

6

eissn

0306-5251

issn

1365-2125

pii

BCP2835

journal_volume

63

pub_type

杂志文章

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