title: Lung deposition from the Turbuhaler in children with cystic fibrosis.
abstract: Drug delivery to patients using dry powder inhalers, such as the Turbuhaler, is believed to be influenced by the inspiratory flow used. Clinical studies have indicated that this delivery system can be used effectively by children. However, it is not known how the total and weight-corrected dose delivered to the airways varies with age. A deposition study using technetium-99m (99mTc)-labelled budesonide was performed in order to determine the effect of age on delivery. Twenty one children with cystic fibrosis, aged 4-16 yrs, were recruited. They were clinically stable with normal lung function. Initially, a gamma camera scan was taken in front of a flood source containing 37 MBq of 99mTc. Subsequently, subjects inhaled through a low resistance inspiratory filter connected to a commercially available Turbuhaler. Immediately afterwards they inhaled from a noncommercial Turbuhaler containing budesonide labelled with 99mTc, and then underwent anterior and posterior gamma camera scans. Both Turbuhaler inhalers were attached to a portable spirometer and the peak inspiratory flow through the Turbuhaler was recorded for each inhalation. The total body dose was calculated from the dose deposited on the inspiratory filter connected to the commercial Turbuhaler. Analysis of the gamma camera images provided information on the proportion of the radiolabel delivered to the lungs compared to that deposited in the upper airway and stomach. As expected, a highly significant positive correlation was noted between the peak inspiratory flow generated by the patient through the Turbuhaler and the dose delivered to the lung. Similarly, there was a highly significant positive correlation between age and "total lung dose". However, when total lung dose was corrected for body weight, there was a nonsignificant negative correlation with age. This study suggests that the "weight-corrected lung dose" achieved when children aged > 6 yrs use the Turbuhaler, is largely independent of age. It would appear that the flow-dependent properties of this device are such that the reduced peak inspiratory flow generated by younger children results in a lower dose to the lungs, but that this is off-set by their lower body weight. This is unlikely to be a property of other devices with different flow/drug delivery characteristics.
authors.affiliation: Dept of Respiratory Medicine, Sheffield Children's Hospital, UK.
authors.forename: S G
authors.initials: SG
authors.lastname: Devadason
authors.forename: M L
authors.initials: ML
authors.lastname: Everard
authors.forename: C
authors.initials: C
authors.lastname: MacEarlan
authors.forename: C
authors.initials: C
authors.lastname: Roller
authors.forename: Q A
authors.initials: QA
authors.lastname: Summers
authors.forename: P
authors.initials: P
authors.lastname: Swift
authors.forename: L
authors.initials: L
authors.lastname: Borgstrom
authors.forename: P N
authors.initials: PN
authors.lastname: Le Souëf
mesh_terms: D000293:Adolescent; D019819:Budesonide / Q000008:administration & dosage / Q000493:pharmacokinetics; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007320:Inspiratory Capacity; D008168:Lung / Q000378:metabolism*; D008297:Male; D009330:Nebulizers and Vaporizers; D009960:Oropharynx / Q000378:metabolism; D010316:Particle Size; D013667:Technetium
chemical_list: D019819:Budesonide; D013667:Technetium