STUDIES ON THE PERSISTENCE OF BASIC AMINES IN THE RABBIT LUNG

  • 1 January 1979
    • journal article
    • research article
    • Vol. 7  (6) , 420-424
Abstract
The time-course of the pulmonary deposition of imipramine (IMIP) following a single i.v. injection into rabbits was investigated. A pool of IMIP and its demethylated metabolites, which exhibited considerable persistence (half-life of decay .simeq. 4 h), was formed in the lung. This pool, now called the slowly effluxable pool (SEP), appears to be synonymous with the noneffluxable pool (NEP), which was previously shown to be formed with IMIP in the isolated perfused lung (IPL). This pool appears to be responsible for the pulmonary persistence of IMIP, inasmuch as 24 h after an i.v. injection it contributes > 90% of the total lung concentration. Chlorphentermine and methadone formed SEP in the IPL of comparable size to that formed with IMIP, but phentermine formed a considerably smaller SEP. Apparently the degree of hydrophobicity of the amine is an important determinant of the size of the SEP formed. This is 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.