Drug Metabolism and Enzyme Kinetics in the Lung
Inhalation as a noninvasive alternative to oral drug administration offers several advantages in drug absorption. The lung is the only organ, other than the heart, through which the entire cardiac output passes. Drug absorption is regulated by a thin alveolar-vascular permeability barrier, which, in parts of the alveolar region, shows an air-blood pathway of less than 0.5m (1). In the adult human lung, the number of alveoli in the deep airway ranges from 200 million to 600 million, resulting in an enormous epithelial surface area that has an estimated value of 140 m2. While these properties are uniquely adapted to promote gas exchange through passive diffusion, they also provide a mechanism for efficient transport of drugs from the circulation to lung tissues and from lung tissues to the bloodstream. Drugs that are administered intravenously may accumulate in high concentrations in the lung following the first passage. On the other hand, the pulmonary epithelium may allow systemic absorption of aerosolized drugs manifold faster than the gastrointestinal tract (2). Thus, there is a great potential that many drug therapies may be improved via inhalation drug delivery, pending further advances in aerosol technology.