Effect of oxygen toxicity and nitric acid-induced lung damage on drug absorption from the rat lung

To investigate the effect of pulmonary oxygen toxicity and nitric acid-induced lung damage on absorption of drugs from the lung, rats were either exposed continuously to approximately 100% oxygen or given an intratracheal injection of 1% nitric acid solution (0.15 ml), and rates of drug absorption from damaged and control lungs were compared after various times. To measure pulmonary absorption rates, 0.1 ml of drug solution (0.1-10 mM) was administered through a tight-fitting tracheal cannula to anesthetized animals, and, after various times, lungs were assayed for unabsorbed drug. Drugs investigated were procaine amide ethobromide, p-aminohippuric acid, procaine amide and mannitol-14C. Rates of drug absorption were increased 1.1-1.2 fold after 48-54 hrs of continuous oxygen exposure and 1.3-1.6 fold at 1-4 days after nitric acid treatment. The results suggest that both types of lung damage increase the porosity of the absorbing membrane, and that nitric acid damage also alters the integrity of lipoid regions of the membrane.