TISSUE DISTRIBUTION AND METABOLISM OF DRUGS. III. ACCUMULATION OF DRUGS BY THE ISOLATED PERFUSED RAT LUNG

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1. The lung accumulation of various drugs has been monitored in the isolated blood-perfused rat lung with artificial ventilation, and the effects of many physiological conditions on the drug accumulation have been investigated. 2. The measurement of the drug disappearance from the perfusate and drug concentration ratio in the lung to the perfusate indicated that many cationic drugs could be concentrated in the lung. In the series of cationic drugs, partition coefficients of drugs were correlated well with drug accumulation by the lung. From these results, it was suggested that the cationic (mainly amino) group as well as the lipophilic group in a molecule were required for lung accumulation of drugs. 3. The concentration ratio of many cationic drugs in the lung to plasma concentration of unbound drugs decreased with increasing concentration of perfusate, and the small contribution of drug partition into the lipoidal component in the lung was observed in the process of drug accumulation. These results indicated that the accumulation of cationic drugs resulted from its saturable and specific binding.