Deposition Patterns of Nebulized Drugs: Is the Pattern Important?

It is logical to assume that the efficacy of an aerosolized drug should be related to the local airway dose. To test this assumption, it is necessary to have some index of the distribution of deposited drug within the airway and a measure of efficacy. However, most studies, in which the regional disftribution of a deposited radiolabeled aerosol throughout the lung has been carefully measured, have not been directly related to the efficacy of any drug. For example, the deposition pattern is critical in terms of interpreting studies of mucociliary clearance but, in those cases, the radiolabel is usually not tied to a therapeutic agonist. Most classical studies measuring the efficacy of an aerosolized drug involve bronchodilators. While bronchodilatation itself has been shown to affect subsequent regional ventilation and particle deposition, targeting specific airways has never been shown to be critical for bronchodilator efficacy. This situation may be different for agents which have a more delayed effect; for example, aerosolized steroids and antibiotics. Little data are available that directly address this question. We have developed techniques for measuring total and regional lung deposition for purposes of addressing the issue of airway site versus drug efficacy. Presently, we have information on methacholine, which is useful for measurement of airway reactivity, gentamicin, pentamidine and cyclosporin. While many factors affect total and regional deposition, we have found that the underlying disease process in the lung is a major determinant of the final deposition pattern. Whether the efficacy of the aerosolized agent is determined by these factors remains to be seen.