Accumulation Mechanism of Basic Durgs in the Isolated Perfused Rat Lung

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The mechanism of the accumulation of basic drugs was investigated by isolated rat lung perfusion. Treatment with various metabolic inhibitors or non-basic drugs did not affect the accumulation of a basic drug in the lung, but a second basic drug inhibited the accumulation of the first basic drug depending on its lipid solubility. The basic durg already accumulated was rapidly displaced by the second drug except for poorly lipid-soluble basic drugs and non-basic drugs. The ability of a second basic durg ot displace the first basic durg was well correlated with its ability to inhibit accumulation. From the Scatchard plot, at least two independent sets of binding sites for basic drugs were found to be present in the isolated perfused lung. The maximum binding capacity for each basic drug was similar in both sites. These results indicate that specific common binding sites for basic drugs, which do not contribute to the active transport system, exist in the lung tissues and the affinity to the sites depends on the lipid solubility of the basic drugs.
公益社団法人日本薬学会の論文
1989-02-25