In vivo measurements of aerosol dose and distribution: Clinical relevance

Mathematical and in vitro models, that incorporate particle diameter, normal breathing frequencies and tidal volumes, have been used to predict the deposition fraction of respirable aerosols within the lungs. Although very useful in drug development, determinations of dose and the distribution of dose based solely on such models may be less accurate than in vivo measurements, which are performed under conditions that combine the effects of all the factors that determine aerosol deposition, including the effect of disease. Gammascintigraphy provides a method for in vivo quantification of the total deposited fraction and the distribution of the dose within the lower respiratory tract. Using this technology, it has been shown that deposition fraction in the lower respiratory tract may vary between 1-30% of the dose actuated from an MDI or nebulizer. This wide range in deposited dose suggests that variations in the clinical response to inhaled aerosols may be explained by alterations in the dose delivered, especially if the aerosolized medication has a narrow therapeutic range. Alterations in the distribution of inhaled drugs within the lungs may also affect the clinical response, such that some disorders may best be treated by targeting drug to specific locations of the lung, while others may respond best to homogeneous distribution of aerosolized drug. In vivo measurements would provide confirmation of the dose deposited as well as the pattern of distribution, which should improve the therapeutic outcome of most aerosolized medications.