Studies on the persistence of basic amines in the rabbit lung.

We have investigated the time-course of the pulmonary deposition of imipramine (IMIP) following a single iv injection into rabbits. A pool of IMIP and its demethylated metabolites, which exhibited considerable persistence (half-life of decay = 4 hr), was formed in the lung. This pool, now called the slowly effluxable pool (SEP), appears to be synonymous with the noneffluxable pool (NEP), which we have previously shown to be formed with IMIP in the isolated perfused lung (PL). Furthermore, this pool appears to be responsible for the pulmonary persistence of IMIP, inasmuch as 24 hr after an iv injection it contributes greater than 90% of the total lung concentration. Chlorphentermine and methadone formed SEP's in the IPL of comparable size to that formed with IMIP, whereas phentermine formed a considerably smaller SEP. These results suggest that the degree of hydrophobicity of the amine is an important determinant of the size of the SEP formed. This further supported by the lack of an SEP with the relatively polar amines, 5-hydroxytryptamine and amphetamine. The 10-fold difference in the size of the SEP for compounds known to induce pulmonary phospholipidosis (chlorphentermine and IMIP) and known not to induce lipidosis (phentermine and amphetamine) may suggest a possible involvement of the SEP in the onset of phospholipidosis; this possibility is discussed.