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

A G Wilson, R D Pickett, T E Eling

    Drug Metabolism and Disposition: the Biological Fate of Chemicals
    |November 1, 1979
    PubMed
    Summary

    A persistent lung pool of imipramine (IMIP) and its metabolites, termed the slowly effluxable pool (SEP), was identified in rabbits. This SEP significantly contributes to IMIP

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    Area of Science:

    • Pharmacokinetics
    • Pulmonary Drug Deposition
    • Toxicology

    Background:

    • The lung's capacity to retain drugs and their metabolites is crucial for understanding drug disposition and potential toxicity.
    • Previous studies indicated a non-effluxable pool (NEP) of imipramine in isolated perfused lungs.

    Purpose of the Study:

    • To investigate the time-course and characteristics of imipramine pulmonary deposition after intravenous injection in rabbits.
    • To identify and characterize the persistent drug pool in the lung and its relationship to drug hydrophobicity and phospholipidosis.

    Main Methods:

    • Intravenous injection of imipramine into rabbits.
    • Quantification of imipramine and its metabolites in lung tissue over time.
    • Comparison of slowly effluxable pool (SEP) formation with other amine compounds.

    Main Results:

    • A slowly effluxable pool (SEP) of imipramine and its metabolites was formed in rabbit lungs, persisting for at least 24 hours.
    • The SEP accounted for over 90% of the total lung imipramine concentration 24 hours post-injection.
    • SEP size correlated with amine hydrophobicity, with chlorphentermine and methadone forming larger pools than phentermine, 5-hydroxytryptamine, and amphetamine.

    Conclusions:

    • The slowly effluxable pool (SEP) is a key factor in the pulmonary persistence of imipramine.
    • Amine hydrophobicity is a significant determinant of SEP formation.
    • The substantial SEP in compounds known to induce pulmonary phospholipidosis suggests a potential role in the pathogenesis of this condition.

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