The Influence of Lung Deposition on Clinical Response

Abstract

Delivery of more drug to the lung may appear to be a desirable goal in the treatment of asthma and chronic obstructive pulmonary disease, since only 10 to 15% of a drug dose administered via a metered dose inhaler (MDI) reaches the lung. However, increasing the dose of most inhaled drugs may only lead to an increase in side effects, since maximal clinical benefit is usually obtained with the currently recommended dosages. Improving the regional deposition of inhaled drugs may be a more effective way of modifying clinical response. Particle size is the most significant determinant of the deposition pattern of inhaled drugs. Optimum drug delivery to the conducting airways occurs with particles ranging from 2.5 to 6 μm; particles <2.5 μm are deposited mainly in the alveoli where they may exert no pharmacodynamic effect and are rapidly absorbed, increasing the risk of systemic adverse events. Delivery devices can be compared by estimating the lung and systemic exposures, taking into account the efficacy and safety dose-response relationships for the drug-device combination. Current devices have profoundly different lung deposition profiles that could affect clinical efficacy when switching devices. Devices that achieve a high lung to systemic ratio for the inhaled drug are preferable.