Species comparison of drug absorption from the lung after aerosol inhalation or intratracheal injection.

To compare the rates of pulmonary absorption of aerosolized and intratracheally injected drugs in the mouse, rabbit, and rat, anesthetized mice and rabbits prepared with a tracheal cannula inhaled a liquid aerosol or received an intratracheal injection of a drug solution by methods previously used in studies on the rat. Aerosols had mass median aerodynamic diameters in the range of 2.28-3.10 microm and geometric standard deviations in the range of 2.35-2.81. The volumes of solution injected intratracheally were approximately 2% of lung volume. At various times after drug administration, the lungs were removed and assayed for unabsorbed compound. Although the 12 drugs studied had widely different absorption rates, each was absorbed approximately 2 times more rapidly when inhaled as an aerosol than when administered by intratracheal injection, suggesting that absorption may be more rapid from the alveolar region than from the tracheobronchial region of the lung. With lipid-insoluble drugs, such as urea, benzylpenicillin, p-aminohippuric acid, mannitol, N-acetylprocainamide ethobromide, sucrose, and inulin, each was absorbed roughly 2.5 times faster in the mouse than in the rat, and roughly 2.5 times more slowly in the rabbit than in the rat. In contrast, with lipid-soluble drugs, such as antipyrine, salicylic acid, barbital, amitrole and procainamide, each was absorbed at about the same rate in all three species. The results suggest that the porosity of the pulmonary membrane is greatest in the mouse, lower in the rat, and lowest in the rabbit. The observed interspecies relationships in absorption rates suggest that it may be possible to predict the rate of absorption of a given drug in one species from data obtained for the same drug in another species.