Comparison of pulmonary accumulation of pyrilamine and pyrilamine N-oxide.

Our previous studies have indicated that a phenothiazine drug, chlorpromazine, and a tricyclic antidepressant, imipramine, are metabolized by the isolated perfused rat lungs via N-oxidation from whence their N-oxides are released into the circulation. This work was undertaken to compare the pulmonary accumulation of another pneumophilic tertiary amine drug, pyrilamine, with that of its N-oxide. Approximately 10-fold greater accumulation of pyrilamine than that of its N-oxide was observed in the mouse lung after a single pass perfusion with 40 microM of the drug for a 3 min period. The largest difference between accumulation of pyrilamine and its N-oxide was noted in the lung among the various tissue slices tested, suggesting the tissue specificity of affinity.