METABOLISM AND ELIMINATION OF INHALED DRUGS AND AIRBORNE CHEMICALS FROM THE LUNGS

Inhalation is a common route by which people are exposed to many toxic chemicals. Inhaled chemicals can deposit in various regions of the respiratory tract. The factors that determine deposition site include chemical reactivity and water solubility for gases and vapors, and shape, physical size, and density for particles. Metabolic activation of chemicals by respiratory tract tissues may play an important role in both the pathogenesis of diseases in these tissues or in modifying the effective dose to tissues distal to the respiratory tract. This paper is a review of the state-of-the-knowledge regarding the regional distribution of xenobiotic metabolizing enzymes in the conducting airways and pulmonary tissue of several animal species, including humans. All segments of the respiratory tract, including the periphery of the pulmonary compartment, contain enzymes (Phase I and II) that metabolize xenobiotic compounds. In general, the data indicate that the pulmonary tissue has a higher metabolic activity toward inhaled chemicals than other regions of the respiratory tract, such as the trachea and bronchi. However, even within an anatomical region of the respiratory tract, there is a non-uniform distribution of enzymes within the individual cell types. Significant species differences exist in metabolic activity toward a number of substrates. However, some generalities can be made. Firstly, the ratio of activating/inactivating enzyme activities in all species is, in general, less than 1. A second point is that this ratio is considerably higher in rodent animal species than humans. This indicates that caution needs to be exercised when extrapolating metabolic data derived from rodents to human metabolic capability.