Perspectives on Lung Dose and Inhaled Biomolecules

Dose is highly important to studies of inhaled agents because there must be an understanding of the dose delivered to humans, the dose delivered to animals in toxicology studies, and an ability to interpret and compare both sets of information relative to safety. Unlike oral or intravenous administrations, total delivered or inhaled dose is not easy to determine following inhalation exposure and is also not necessarily the most important determinant of toxicity. A review of dose distribution throughout the respiratory tract as well as total inhaled dose is provided. The implications of regional deposition for biologics are reviewed and specific examples over a range of different molecular weights are provided. Biologics are generally large enough that absorption from ciliated epithelia is low. Thus, deposition of biologics in head airways and tracheobronchial regions is unlikely to be of high importance unless there are interactions with specific receptors at these sites. Therefore, it is the dose of proteins or biologics deposited in the alveolar region that are generally of most interest.