Deposition of Foradil P in human lungs: comparison of in vitro and in vivo data.

In order to characterize the efficacy of dry powder inhalers, in vitro measurements are much easier to perform than human deposition studies, especially in early stages of drug development. In this study, lung deposition and delivered dose of radiolabeled Foradil P inhaled with the Aerolizer were measured in 10 healthy subjects. These data were then compared with data derived from an in vitro assessment of the device output and particle size distribution combined with mathematical modeling of lung deposition (modified ICRP-model). Delivered dose and lung deposition increased slightly but statistically significant with the inhalation peak flow in both the in vivo data and the in vitro data. The delivered dose ranged from 60% to 80% and lung deposition, relative to the fill weight, from 13% to 28%. Differences between the in vitro and in vivo data were slight and statistically not significant. This study indicates that in vitro assessment of device performance, in combination with lung deposition delivery data, are in good agreement with deposition data measured in healthy subjects. Since there was only a slight flow rate dependency of lung deposition without clinical relevance, it may additionally be concluded that the Aerolizer is a robust, easy to handle inhalation device with stable and reproducible drug delivery characteristics.

Towards an inhalative 13C breath test method.

Customary 13CO2 breath tests--and also 15N urine tests--always start with an oral administration of a test substrate. The test person swallows a stable isotope labelled diagnostic agent. This technique has been used to study several pathophysiological changes in gastrointestinal organs. However, to study pathophysiological changes of the bronchial and lung epithelium, the inhalative administration of a stable isotope labelled agent appeared more suitable to us. [1-13C]Hexadecanol and [1-13C]glucose were chosen. Inhaled [1-13C]hexadecanol did not yield 13CO2 in the exhaled air, but [1-13C]glucose did. To study the practicability of the [1-13C]glucose method and the reproducibility of the results, 18 inhalation tests were performed with healthy subjects. In 6 self-tests, the optimum inhalative dose of [13C]glucose was determined to be 205 mg. Using the APS aerosol provocation system with the nebulizer 'Medic Aid' (Erich Jaeger Würzburg), a 25% aqueous solution was inhaled. Then, breath samples were collected at 15 min. intervals and analysed for 13CO2. 75-120 min after the end of inhalation a well-reproducible maximum delta13C value of 6%o over baseline (DOB) was detected for 12 healthy probands. Speculating that the pulmonary resorption of the [13C]glucose is the rate-limiting step of elimination, decompensations in the epithelium ought to be reflected in changed [1-13C]glucose resorption rates and changed 13CO2 output. Therefore, we speculate that the inhalation of suitable 13C-labelled substrates will pave the way for a new group of 13CO2 breath tests aiding investigations of specific pathophysiological changes in the pulmonary tract, such as inflammations of certain sections and decompensations of cell functions.