Integration of computer model of drug delivery with human subject testing

摘要

Mathematical models may be used a priori to determine experimental conditions to facilitate the administration of inhaled pharmacologic drugs. By regulating inhaled particle sizes and patient ventilatory parameters, aerosolized medicines can be targeted to appropriate sites to elicit optimum therapeutic effects. In our clinical laboratory we have employed computer simulations as a methodology to treat respiratory diseases per se, and are presently advocating inhalation as a novel technique for systemic delivery of Pharmaceuticals to other organs. In both types of models, it is imperative that the morphology of the human respiratory system be anatomically realistic. Herein, we report on new computational techniques to describe lung structures as affected by airway diseases. Asthma will be the representative case. We have simulated airway narrowing due to inflammation and bronchoconstriction by varying airway diameters in a systematic manner, consistent with clinical observations. Tracheobronchial (TB) diameters were reduced (relative to healthy control conditions) by 20 and 40%. Moreover, the regional manifestation of asthma in the upper, middle and lower airways of the TB compartment was described separately. The results indicate that the severity of disease, patient ventilation and inhaled particle size, have systematic effects on drug deposition sites. In a real sense, therefore, targeted delivery achieved via computer simulations, enhances the efficacy of an inhaled pharmacologic drug.