Subcellular distribution of basic drugs accumulated in the isolated perfused lung.
To clarify the mechanism by which basic drugs accumulate in the lung, the binding selectivity of drugs to different subcellular structures of the perfused rat lung was examined. Imipramine, quinine, and metoclopramide were used as examples of basic drugs. The accumulation of basic drugs was highest in the mitochondrial fraction. The drug accumulation in the lung mitochondrial fraction increased with increasing lipid solubility and was dose dependent. These results suggest the presence of specific binding sites for basic drugs in mitochondria and that mitochondria play an important role as a reservoir for basic drugs.
D000818:Animals; D007099:Imipramine / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D050356:Lipid Metabolism; D008168:Lung / Q000378:metabolism*; D008297:Male; D008787:Metoclopramide / Q000493:pharmacokinetics; D010477:Perfusion; D010599:Pharmacokinetics; D011803:Quinine / Q000493:pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains; D012995:Solubility; D013347:Subcellular Fractions / Q000378:metabolism*
D011803:Quinine; D008787:Metoclopramide; D007099:Imipramine