Large differences in lung deposition between dry powder inhalers in children

Turbuhaler was found to deposit almost four times as much of the inhaled steroid budesonide (Pulmicort®) in the lungs compared to Diskus with the corresponding drug fluticasone (Flixotide®). In addition there was a more than two fold higher variability in dose delivery to the lungs with Diskus.

The lung deposition study was conducted in 15 children aged 8-14 years. The children had mild asthma and inhaled similar nominal doses of the two drugs, which was followed by measurements of plasma concentrations, preventing gastrointestinal absorption with charcoal. For reference values both drugs were also given intravenously. The absorption from the lungs – which is assumed to equal lung deposition – after inhalation from Turbuhaler was calculated to be 30.8% and 8% from Diskus, with a co-efficient of variation of 24 and 61% for the two inhalers respectively.

In the comment to the study results Danish investigators Lone Agertoft and Søren Pedersen acknowledge that the higher variability in lung deposition from Diskus was unexpected as several in-vitro investigations of the two inhalers have shown the opposite result.

- The implication of this is that clinicians should not put too much emphasis on in-vitro comparisons of variability of drug delivery of different inhalers since they may be poor predictors of what happens in-vivo, professor Pedersen states.

The large difference in overall lung deposition between the two inhalers is known from earlier studies in adult patients, and probably reflects the difference in the fraction of respirable particles.

- The study shows that some children using Diskus will only obtain 3-4% of the nominal dose of fluticasone from the inhaler, and that most part of the drug will be deposited outside the airways. Overall, this may affect both the clinical efficacy and side-effect profile of the preparation, professor Pedersen says.

Further enquires to:

Søren Pedersen
Department pf Paediatrics
Kolding Hospital
DK-6000 Kolding
Tel +45 40 28 86 04

References
Agertoft L and Pedersen S. Lung deposition and systemic availability of fluticasone Diskus and budesonide Turbuhaler. American Journal of Respiratory and Critical Care Medicine 2003; 168;(7) October 1st.

Bisgaard H, Klug B, Sumby BS, Burnell PK. Fine particle mass from the Diskus inhaler and Turbuhaler inhaler in children with asthma. European Respiratory Journal 1998;11(5):1111-5.

Thorsson L, Edsbäcker S, Källén A, Löfdahl CG. Pharmacokinetics and systemic activity of fluticasone via Diskus® and pMDI, and of budesonide via Turbuhaler®. British Journal of Clinical Pharmacology 2001;52(5):529-38