EFFECT OF DESMETHYLIMIPRAMINE ON THE KINETICS OF CHLORPHENTERMINE ACCUMULATION IN ISOLATED PERFUSED RAT LUNG

  • 1 January 1979
    • journal article
    • research article
    • Vol. 211  (3) , 514-518
Abstract
A number of basic amines are preferentially accumulated by the lung, and there is the possibility that drug interactions in this organ may be important in vivo. The kinetics of the accumulation process for chlorphentermine were examined in a single pass isolated perfused rat lung. Chlorphentermine (2.5 .times. 10-7-2.5 .times. 10-5 M) was rapidly taken up over the 10 min perfusion period, and the rate uptake was well described by a biexponential equation. One component of the uptake was small in capacity and nonsaturable while the other was large in capacity and saturable. The smaller component could not be explained solely by distribution into total lung water. When demethylimipramine (10-6-10-3 M) was added to the perfusate, it had little effect on the nonsaturable component but markedly affected the other; the initial velocity of uptake was decreased and the (negative) rate of change of uptake was increased with increased demethylimipramine concentration. There were at least 2 mechanisms involved in uptake of chlorphentermine: a saturable transport process and tissue binding. It is not clear whether the transport saturability is a manifestation of a carrier-mediated process or of drug-induced membrane changes affecting diffusion.

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