Mathematical model for the selective deposition of inhaled pharmaceuticals

Abstract

To accurately assess the potential therapeutic effects of airborne drugs, the deposition sites of inhaled particles must be known. Herein, an original theory is presented for physiologically based pharmacokinetic modeling and related prophylaxis of airway diseases. The mathematical model describes the behavior and fate of particles in the lungs of adult human subjects under various breathing conditions. Their deposition patterns are calculated via superposition of the separate but not independent processes of inertial impaction, sedimentation, and diffusion. The related computer code is designed to calculate total and compartmental (tracheobronchial and pulmonary) distributions of inhaled aerosols. In this manuscript, the model is first tested via comparisons of predicted deposition patterns with laboratory data from human inhalation exposure experiments and then it is applied to determine which factors most influence the dosimetry of inhaled particles. In this format, deposition patterns are explicitly related to particle characteristics, ventilatory parameters, and intersubject variabilities of lung morphologies. The dosimetric model was developed to improve the efficacy of aerosol therapy via the selective deposition of inhaled pharmaceuticals at prescribed lung locations to elicit optimum effects.