title: Site of deposition and absorption of an inhaled hydrophilic solute.
abstract: OBJECTIVE
  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.affiliation: AstraZeneca R and D Lund, SE-22187 Lund, Sweden. Eva.Bondesson@astrazeneca.com
authors.forename: Eva
authors.initials: E
authors.lastname: Bondesson
authors.forename: Thomas
authors.initials: T
authors.lastname: Bengtsson
authors.forename: Lars-Erik
authors.initials: LE
authors.lastname: Nilsson
authors.forename: Per
authors.initials: P
authors.lastname: Wollmer
mesh_terms: D000042:Absorption; D000280:Administration, Inhalation; D000328:Adult; D000336:Aerosols / Q000008:administration & dosage*; D002614:Chelating Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D006801:Humans; D008168:Lung / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009079:Mucociliary Clearance; D016284:Technetium Tc 99m Pentetate / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014057:Tomography, X-Ray Computed / Q000379:methods
chemical_list: D000336:Aerosols; D002614:Chelating Agents; D016284:Technetium Tc 99m Pentetate