Al. Coates et al., Accounting for radioactivity before and after nebulization of tobramycin to insure accuracy of quantification of lung deposition, J AEROSOL M, 13(3), 2000, pp. 169-178
Citations number
30
Categorie Soggetti
Envirnomentale Medicine & Public Health
Journal title
JOURNAL OF AEROSOL MEDICINE-DEPOSITION CLEARANCE AND EFFECTS IN THE LUNG
The ability to predict drug deposition of inhaled drugs used in cystic fibr
osis (CF) is important if there is a need to target specific doses of drug
to the lungs of individual patients. The gold standard of measuring pulmona
ry deposition is the quantification of an aerosolized radiolabel either mix
ed with the drug solution or tagged directly to the compound of interest. A
ccuracy of the quantification could be assured if there is agreement betwee
n the amount of radioactivity before and after administration. Before admin
istration, the radiolabel is concentrated in the well of the nebulizer, whe
reas after administration, it is distributed throughout the nebulizer, the
expiratory filter and connectors, and the upper airway, stomach, trachea, a
nd lung. Not only is the geometry of the distribution that is presented to
the gamma camera different, but there are different attenuation factors for
the various body tissues. The primary aim of this study was to evaluate th
e accuracy of the quantification of deposition. Secondary goals were to com
pare in vitro nebulizer performance with that measured in vivo during the d
eposition study. Eighty milligrams of tobramycin and technetium bound to hu
man serum albumin was administered to 10 normal adults using a Pari LC Jet
Plus (Pari Respiratory Equipment, Inc., Richmond, VA) breath-enhanced nebul
izer. Techniques were developed that allowed for the accounting of 99 +/- 2
% of the initial radioactivity. The fraction of the rate of lung deposition
to total body deposition was the in vivo respirable fraction (0.62 +/- 0.0
7), which closely agreed with in vitro measurements of respirable fraction
(0.62 +/- 0.04). Drug output measured from the change in weight and concent
ration in the nebulizer systematically overestimated drug output measured b
y the deposition study. The results indicate that 11.8 of the initial 80 mg
would be deposited in the lungs. This technique could be adapted to accura
tely quantify the amount of deposition on any inhaled therapeutic agent, bu
t caution must be used when extrapolating performance of a nebulizer on the
bench to expected deposition in patients.