title: The pulmonary deposition of two aerosol preparations of nedocromil sodium delivered by MDI assessed by single photon emission computed tomography.
abstract: The pulmonary deposition and pharmacokinetics of fine and coarse radioactive aerosols of nedocromil sodium, of mass median aerodynamic diameters 16 microns and 24 microns respectively, delivered by metered dose inhaler (MDI) have been investigated. The corresponding geometric standard deviations of the particle size distributions were 5.32 and 3.93. Pulmonary deposition was assessed by both planar radionuclide scintigraphy and multi-modality three dimensional imaging using single photon emission computed tomography (SPECT) and x-ray computed tomography (CT). The three dimensional data were analysed by transformation to a hemispherical shape based on the fractional radial distance of each point in the lung from the centre to the corresponding extrapolated point on the periphery. This enabled parameters on the variation of both concentration of deposition and total amount deposited with penetration distance to be calculated. For both planar and SPECT data the central to peripheral concentration ratio (C/P ratio) was calculated. The three dimensional C/P ratio showed a median value (3.21) which was significantly higher than for the planar imaging (2.03) (p < 0.001). The parameter used to express the variation of total amount deposited was the median dose position. This showed that for both aerosols 50% of the dose was deposited at sites with a percentage central to peripheral distance of greater than 68%. There was a trend for total percentage of the fine aerosol in the lungs to be higher than for the coarse and for its deposition to be more peripheral. In addition the mean concentrations in blood were measured to be greater for the fine aerosol. However these differences were relatively small and none were individually statistically significant. The technique of combined SPECT and CT imaging was shown to be valuable in obtaining more accurate information on pulmonary distribution of inhaled aerosol deposition. The merits, limitations and potential applications of the technique are discussed.
authors.affiliation: Immunopharmacology Group, University of Southampton, UK.
authors.forename: Q A
authors.initials: QA
authors.lastname: Summers
authors.forename: J S
authors.initials: JS
authors.lastname: Fleming
authors.forename: Y
authors.initials: Y
authors.lastname: Dai
authors.forename: S
authors.initials: S
authors.lastname: Perring
authors.forename: R
authors.initials: R
authors.lastname: Honeywell
authors.forename: K J
authors.initials: KJ
authors.lastname: Gough
authors.forename: A G
authors.initials: AG
authors.lastname: Renwick
authors.forename: A R
authors.initials: AR
authors.lastname: Clark
authors.forename: M A
authors.initials: MA
authors.lastname: Nassim
authors.forename: S T
authors.initials: ST
authors.lastname: Holgate
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000336:Aerosols / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008168:Lung / Q000000981:diagnostic imaging*; D008297:Male; D009330:Nebulizers and Vaporizers; D017835:Nedocromil / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010316:Particle Size; D013667:Technetium; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed / Q000379:methods