Improvement of intestinal absorption of P-glycoprotein substrate by D-tartaric acid.
Improvement of intestinal absorption of P-glycoprotein substrate by D-tartaric acid.
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D-酒石酸改善肠道对 P-糖蛋白底物的吸收。
DOI：
10.2133/dmpk.21.424
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发表时间：
2006
影响因子：
2.1
通讯作者：
M. Hayashi
中科院分区：
文献类型：
--
作者：
A. Iida;M. Tomita;Yoko Idota;Y. Takizawa;M. Hayashi
本实验的目的是在原位和体外实验条件下研究D-酒石酸（TA）对药物在肠吸收的影响。在体外扩散室实验中，TA（10 mM）添加到大鼠结肠粘膜侧显着降低罗丹明123（Rho 123）从serum到粘膜侧的运输。由于TA已被证明在低pH条件下改变大鼠结肠上皮紧密连接的完整性，从而改善细胞旁药物转运，因此在本研究中，在pH 7.4下检查了TA对膜阻力的影响。结果发现，膜电阻，细胞旁完整性的指标，在pH 7.4没有变化。在原位循环方法中，TA（20 mM）增加了Rho 123在回肠和结肠中的吸收，但在空肠中没有。TA（20 mM）也增加了柔红霉素在回肠的吸收，但TA（20 mM）没有改变P-糖蛋白（P-gp）的表达水平。TA（20 mM）显著抑制i. v. -将Rho 123和柔红霉素施用到回肠腔中。总之，我们第一次证明了TA增加了P-gp底物Rho 123和柔红霉素的肠道吸收，可能是通过调节P-gp功能而不改变P-gp在大鼠肠道中的表达水平。
The purpose of the present experiment was to examine the effects of D-tartaric acid (TA) on intestinal drug absorption under both in situ and in vitro experimental conditions. In the in vitro diffusion chamber experiments, TA (10 mM) added to the mucosal side of rat colon significantly decreased rhodamine123 (Rho 123) transport from the serosal to mucosal side. Since TA has been shown to change the integrity of the epithelial tight junctions in rat colon at low pH conditions, resulting in improved paracellular drug transport, the effect of TA on membrane resistance was examined at pH 7.4 in the present study. It was found that membrane resistance, an indicator of paracellular integrity, did not change at pH 7.4. In the in situ loop method, TA (20 mM) increased the absorption of Rho123 in both ileum and colon but not in jejunum. TA (20 mM) also increased the absorption of daunorubicin in the ileum, but TA (20 mM) did not change the expression level of P-glycoprotein (P-gp). TA (20 mM) significantly inhibited excretion of i.v.-administered Rho123 and daunorubicin into the ileal lumen. In conclusion, for the first time we demonstrated that TA increases the intestinal absorption of P-gp substrates Rho123 and daunorubicin, possibly by modulating the P-gp function without changing the expression level of P-gp in the rat intestine.
影响因子：
3.3
作者：
Kitagawa, S;Nabekura, T;Kamiyama, S
通讯作者：
Kamiyama, S