In Situ and in Vitro Evidence for Stereoselective and Carrier-Mediated Transport of Monocarboxylic Acids across Intestinal Epithelial Tissue

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The present study was designed to establish the significance of carrier-mediated transport in the intestinal absorption of monocarboxylic acids by examining the stereoselectivity of transepithelial transport of chiral monocarboxylic acids. The transport of L- and D-lactic acids was examined in vitro using rat intestinal tissue sheets and in situ by means of intra-jejunal administration, followed by measurement of the plasma concentration. Both the absorptive and secretory transport of L-[^<14>C]lactic acid across the intestinal epithelial tissues of rats was significantly greater than that of the D-isomer. The secretory transport of the L-isomer was significantly greater than the absorptive transport, implying ne transport in the secretory direction. When L- and D-[^<14>C]lactic acids wre administered to the rat jejunum, the absorption ratio of the L-isomer was lower than that of the D-isomer at 15 min after administration. The concentration-dependence of absorption for both L- and D-[^<14>C]lactic acids indicated the involvement of both saturable and nonsaturable processes. The saturable process showed a higher affinity and lower capacity for L-lactic acid compared with the D-isomer, while no significant difference between the isomers was observed in the nonsaturable process. The absorption of L-lactic acid was inhibited by chiral 2-hydroxymonocarboxylic acids in a stereoselective manner. Chiral monocarboxylic acids were shown to cross the intestinal epithelial tissues and to be absorbed in a stereoselective manner after oral administration, suggesting the involvement of specific carrier-mediated transport mechanism(s) in their intestinal absorption in vivo.
公益社団法人日本薬学会の論文
2000-07-01

In Situ and in Vitro Evidence for Stereoselective and Carrier-Mediated Transport of Monocarboxylic Acids across Intestinal Epithelial Tissue

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