Assessment of drug disposition in the lung

Airway disposition of drugs is assessed with either physiological changes in lung mechanics or nuclear scanning of the tagged medication. Several methods have been described for assessment of the pulmonary disposition of drugs delivered by routes other than the airways. These methods include tissue biopsy and sputum analysis of pooled secretions and tracheal washings. More recently, bronchoalveolar lavage fluid has been analysed for a variety of pharmacological agents and comparisons drawn between blood and lavage supernatant levels. Problems in correcting for dilution have been overcome by using a naturally occurring tracer substance, such as creatinine or albumin, which has a similar molecular weight to the test chemicals and which can be assayed readily in blood and lavage fluid. It has become apparent that neither naturally occurring not exogenous chemicals enter the lung in a concentration that is predictable from their levels in the blood. While the alpha 2-macroglobulin level in lavage fluid is approximately 25 times less than that in serum, a 1:1 relationship exists for alpha 1-antitrypsin. Cortisol achieves a concentration in lung fluid equal to that of blood, but lung fluid concentrations of methylprednisolone and prednisone are one-half, or at best one-third, of the blood concentration, respectively. Knowledge regarding the penetration of antibiotics into the lung is useful in determining the potential effectiveness of a given agent and its likely acinar MIC. It appears that the alveolar-capillary unit is not freely permeable to all agents, raising the possibility that a blood-lung barrier exists which is responsible for maintaining the alveolar environment. The knowledge that there is a differential permeability among drugs makes it important for clinicians to assess this characteristic of each agent before conclusions linking dose and response are drawn.