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Can Pediatric Throat Models and Air Flow Profiles Improve Our Dose Finding Strategy?

Wachtel H, Bickmann D, Breitkreutz J, Langguth P.

Respiratory Drug Delivery 2010. Volume 1, 2010: 195-204.

Abstract:

In the field of aerosol therapy, early phase pediatric clinical research can be supported or even partly substituted by i) handling studies and ii) in vitro investigations. In vitro methods are described here to enable dose-to-lung predictions in children inhaling from devices designed for adults. These in vitro tests aim to predict the dose to lung (DTL) using mouth/nose-throat models under realistic inhalation flow conditions. Within the range from one to five years of age, a comparison of airway geometries indicates that individual variability is much higher than the variability due to age alone. Therefore it seems possible to select a very small number of relevant throat models (e.g., small and large) to span the likely range. In vitro results presented here, collected using an idealized throat model (approximate age 5 years) indicate that children can achieve DTL=51% of label claim with Respimat and DTL=33% with valved holding chambers combined with Respimat when inhaling orally. Dose delivery to the lung also depends on breathing patterns as well as on aspects of inhaler handling. In sub populations (e.g., very young children) clinical trial settings with low numbers of patients may suffer from high variability because of variability in lung function measurements, inhaler handling and unpredictable dosimetry. This is in contrast to the large studies in adults where key results directly indicate the effect of a treatment. Enhanced in vitro studies may fill some of this gap by providing precise dose information for inhalers and their accessories.