A nonhuman primate aerosol deposition model for toxicological and pharmaceutical studies

Nonhuman primates may be used as human surrogates in inhalation exposure st udies to assess either the (1) adverse health effects of airborne particula te matter or (2) therapeutic effects of aerosolized drugs and proteins. Mat hematical models describing the behavior and fate of inhaled aerosols may b e used to complement such laboratory investigations. For example, the optim al conditions, in terms of ventilatory parameters (e.g., breathing frequenc y and tidal volume) and aerosol characteristics (e.g., geometric size and d ensity), necessary to target drug delivery to specific sites within the res piratory tract may be estimated a priori with models. In this work a mathem atical description of the rhesus monkey (Macaca mulatta) lung is presented for use with an aerosol deposition model. Deposition patterns of 0.01- to 5 -mum-diameter monodisperse aerosols within lungs were calculated for 3 monk ey lung models (using different descriptions of alveolated regions) and com pared to human lung results obtained using a previously validated mathemati cal model of deposition physics. Our findings suggest that there are signif icant differences between deposition patterns in monkeys and humans. The no nhuman primates had greater exposures to inhaled substances, particularly o n the basis of deposition per unit airway surface area. However, the differ ent alveolar volumes in the rhesus monkey models had only minor effects on aerosol dosimetry within those lungs. By being aware of such quantitative d ifferences, investigators can employ the respective primate models (human a nd nonhuman) to more effectively design and interpret the results of future inhalation exposure experiments.