Degree of throat deposition can explain the variability in lung deposition of inhaled drugs

Abstract

Inhalation is a mainstay for treatment of asthma, and lung deposition can be seen as a surrogate marker for the ensuing clinical effects. Not only absolute lung deposition, but also its variability is of interest, as it indicates the range of expected lung deposition in an individual patient when prescribing the drug and the expected day-to-day variability when using it. A literature survey found 71 studies with relevant information on lung deposition and its variability. Further characteristics of the studies, such as if the subjects were healthy or asthmatics, adults or children, and what device that was used, were noted. In all, 187 data points were included. Variability in lung deposition was depicted as a function of mean lung deposition; for the entire data set and for subsets thereof. Independent of device type or subject category high lung deposition was associated with low relative variability and vice versa. Using a published throat deposition model, the observed correlation of lung deposition variability to mean lung deposition could be explained as being determined largely by the extent of and variability in throat deposition. We hypothesize that throat deposition is the major determinant for lung deposition of an inhaled aerosol, and its absolute variability will largely be determined by the absolute variability in throat deposition. The relative variability in lung deposition will therefore tend to be high for low lung deposition and low for high lung deposition. Consequently, low relative variability in lung deposition can only be attained if high lung deposition is achieved.