Effect of size and disease on estimated deposition of drugs administered using jet nebulization in children with cystic fibrosis.
OBJECTIVE
To develop a model that quantified the nebulizer output that was inhaled by subjects with cystic fibrosis (CF) in order to predict the amount of drug likely to enter the upper airway contained in particles small enough to be deposited in the lower respiratory tract of individual patients.


METHODS
Forty-three patients (age, 6 to 18 years) with CF, with FEV(1) of 26 to 124% of predicted, breathed through a nebulizer circuit with a pneumotachograph in place at the distal end. Algorithms were developed from the measured flows through the pneumotachograph, allowing partitioning of inspiration into undiluted aerosol and fresh gas. In order to validate the algorithms, argon was added to the nebulizing gas flow and then its concentration was analyzed at the mouth by mass spectrometry.


RESULTS
Predictions of the concentration of argon at the mouth were concordant with that measured by mass spectrometry, thus validating the model. Combining data from the model with in vitro nebulizer performance data, predictions for estimates for lung deposition for individuals were possible. Total estimate was independent of patient size or FEV(1). The respiratory duty cycle was 0.44 +/- 0.05 (mean +/- SD) and correlated (r = 0.91, p < 0.001) with estimated deposition and minute ventilation (r = 0.60, p < 0.01). However, when expressed in milligrams per kilogram of body weight, the estimated deposition in smaller children was fourfold higher than in larger children.


CONCLUSIONS
If the effect of patient size and pattern of breathing on estimated drug deposition are not considered when prescribing drugs given by nebulization, the result may be overdosing younger children, underdosing older children, or both.
Coates
A L
AL
Division of Respiratory Medicine, Hospital for Sick Children, University of Toronto, Toronto, Canada. allan.coates@sickkids.on.ca
Allen
P D
PD
MacNeish
C F
CF
Ho
S L
SL
Lands
L C
LC
D000280:Administration, Inhalation; D000293:Adolescent; D000336:Aerosols; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001824:Body Constitution; D002648:Child; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000503:physiopathology; D004867:Equipment Design; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008962:Models, Theoretical; D009330:Nebulizers and Vaporizers; D012123:Pulmonary Ventilation; D015656:Respiratory Mechanics; D014031:Tobramycin / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000336:Aerosols; D000900:Anti-Bacterial Agents; D014031:Tobramycin