トランスポーターを介した薬物動態制御

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  • Membrane Transporters as Determinant of Drug Absorption and Disposition.

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Although passive diffusion, which depends on the lipid solubility, is a fundamental mechanism for the membrane transport of many of compounds, water-soluble compounds also cross cell membranes by the specialized carrier-mediated transport mechanisms. We have demonstrated that several drugs are transported by the tissue-specific transporters in intestinal and renal epithelial cells, hepatocytes and brain capillary endothelial cells which form the blood-brain barrier. They include oligopeptide transporter, monocarboxylic acid transporter, anion antiporter, organic anion transporter, and P-glycoprotein. Most of them functions for the uptakes of drugs into the cells leading to the increased permeability, others exclude drugs out of cells, thereby decreasing apparent permeability into cells. It was also found that a certain drug which crosses by the certain transporter in the intestinal membranes is sometimes recognized by the other transporter, or not recognized by transporters in other tissues. This finding demonstrates that it would be possible to expect tissue specific delivery of drugs by utilizing transporters which have different characteristics among tissues. Such a difference in permeability among tissues would be difficult to expect when the membrane transport is carried out by passive diffusion. There are more evidences for carrier-mediated transport of many drugs in various tissues other than mentioned in the present study. Further mechanistic clarification and quantitative analysis of pharmacokinetic importance of such transporters will help the development of effective strategies for the site specific drug delivery.

収録刊行物

  • 薬物動態

    薬物動態 11 (6), 642-650, 1996

    日本薬物動態学会

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