Effect of size and disease on estimated deposition of drugs administered using jet nebulization in children with cystic fibrosis

Study objectives: To develop a model that quantified the nebulizer output t hat was inhaled by subjects with cystic fibrosis (CF) in order to predict t he amount of drug likely to enter the upper airway contained in particles s mall enough to be deposited in the lower respiratory tract of individual pa tients. Design: Forty-three patients (age, 6 to 18 years) with CF, with FEV1 of 26 to 124% of predicted, breathed through a nebulizer circuit with a pneumotac hograph in place at the distal end, Algorithms were developed from the meas ured flows through the pneumotachograph, allowing partitioning of inspirati on into undiluted aerosol and fresh gas. In order to validate the algorithm s, argon was added to the nebulizing gas flow and then its concentration wa s analyzed at the mouth by mass spectrometry, Results: Predictions of the concentration of argon at the mouth were concor dant with that measured by mass spectrometry, thus validating the model, Co mbining data from the model with in vitro nebulizer performance data, predi ctions for estimates for lung deposition for individuals were possible. Tot al estimate was independent of patient size or FEV1. The respiratory duty c ycle was 0.44 +/- 0.05 (mean +/- SD) and correlated (r = 0.91, p < 0.001) w ith estimated deposition and minute ventilation (r = 0.60, p < 0.01). Howev er, 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 esti mated drug deposition are not considered when prescribing drugs given by ne bulization, the result may be overdosing younger children, underdosing olde r children, or both.