Ogihara T, Tamai I, Tsuji A
Department of Pharmacobio-Dvnamics, Faculty of Pharmaceutical Sciences, Kanazawa University, Japan.
Biol Pharm Bull. 2000 Jul;23(7):855-9. doi: 10.1248/bpb.23.855.
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-[14C]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 net transport in the secretory direction. When L- and D-[14C]lactic acids were 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-[14C]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.
本研究旨在通过检测手性一元羧酸跨上皮转运的立体选择性，来确定载体介导转运在一元羧酸肠道吸收中的意义。使用大鼠肠组织片在体外研究了L-和D-乳酸的转运，并通过空肠内给药在原位进行研究，随后测定血浆浓度。L-[14C]乳酸在大鼠肠道上皮组织中的吸收性和分泌性转运均显著大于D-异构体。L-异构体的分泌性转运显著大于吸收性转运，这意味着在分泌方向上的净转运。当将L-和D-[14C]乳酸给予大鼠空肠时，给药后15分钟时L-异构体的吸收比低于D-异构体。L-和D-[14C]乳酸吸收的浓度依赖性表明涉及可饱和和不可饱和过程。与D-异构体相比，可饱和过程对L-乳酸表现出更高的亲和力和更低的容量，而在不可饱和过程中未观察到异构体之间的显著差异。L-乳酸的吸收受到手性2-羟基一元羧酸的立体选择性抑制。手性一元羧酸在口服给药后显示可穿过肠道上皮组织并以立体选择性方式被吸收，这表明在其体内肠道吸收中涉及特定的载体介导转运机制。
