THE PULMONARY DEPOSITION OF 2 AEROSOL PREPARATIONS OF NEDOCROMIL SODIUM DELIVERED BY MDI ASSESSED BY SINGLE-PHOTON EMISSION COMPUTED-TOMOGRAPHY

The pulmonary deposition and pharmacokinetics of fine and coarse radio active aerosols of nedocromil sodium, of mass median aerodynamic diame ters 16 mu m and 24 mu m respectively, delivered by metered dose inhal er (MDI) have been investigated. The corresponding geometric standard deviations of the particle size distributions were 5.32 and 3.93. Pulm onary deposition was assessed by both planar radionuclide scintigraphy and multi-modality three dimensional imaging using single photon emis sion computed tomography (SPECT) and x-ray computed tomography (CT). T he three dimensional data were analysed by transformation to a hemisph erical shape based on the fractional radial distance of each point in the lung from the centre to the corresponding extrapolated point on th e periphery. This enabled parameters on the variation of both concentr ation of deposition and total amount deposited with penetration distan ce to be calculated. For both planar and SPECT data the central to per ipheral concentration ratio (CIP ratio) was calculated. The three dime nsional CIP ratio showed a median value (3.21) which was significantly higher than for the planar imaging (2.03) (p<0.001). The parameter us ed to express the variation of total amount deposited was the median d ose position. This showed that for both aerosols 50% of the dose was d eposited at sites with a percentage central to peripheral distance of greater than 68%. There was a trend for total percentage of the fine a erosol in the lungs to be higher than for the coarse and for its depos ition to be more peripheral. In addition the mean concentrations in bl ood were measured to be greater for the fine aerosol. However these di fferences were relatively small and none were individually statistical ly significant. The technique of combined SPECT and CT imaging was sho wn to be valuable in obtaining more accurate information on pulmonary distribution of inhaled aerosol deposition. The merits, limitations an d potential applications of the technique are discussed.