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TARGETED DELIVERY OF INHALED PHARMACEUTICALS USING AN IN SILICO DOSIMETRY MODEL
Citation:
Martonen, T B., K K. Isaacs, AND J. S. Fleming. TARGETED DELIVERY OF INHALED PHARMACEUTICALS USING AN IN SILICO DOSIMETRY MODEL. Presented at American Thoracic Society, San Diego, CA, May 20-25, 2005.
Description:
We present an in silico dosimetry model which can be used for inhalation toxicology (risk assessment of inhaled air pollutants) and aerosol therapy ( targeted delivery of inhaled drugs). This work presents scientific and clinical advances beyond the development of the original in silico model (Martonen et al., 2003, Ad Drug Del Rev 55:829-849) and its applications in the medical arena (Sbirlea-Apiou et al., 2004, J Pharm Sci93:1205-1216). METHODS: The model of a mathematical description of particle motion within diseased airways and an computer algorithm defining the behavior and fate of inhaled drugs. In silico modeling is an effective scientific tool that can identify the effects of inhaled particle sizes, patient ventilatory parameters, and diseased airway morphologies on drug disposition. The code allows a physician to interactively describe the distribution and magnitude of broncho-constriction and inflammation, thereby permitting computer simulations of treatment via inhaled bronchodilators and steroids. RESULTS AND CONCLUSIONS: To facilitate comparison with experimental data from human subject studies, the calculated disposition of aerosol is determined as total lung deposition and its compartmental discrimination among constituent tracheobronchial (TB) and pulmonary (P) regions. Moreover, to promote the concept of targeted delivery to diseased cellular sites and receptors, we present particle deposition generation-by-generation and at a local level measured in terms of aerosol quantity per unit airway surface area. We suggest that in silico modeling be employed in a complementary manner with asthma-related aerosol therapy protocols. Disclaimer: This is an abstract of a proposed presentation and does not reflect EPA policy.