Yamamoto A, Uchiyama T, Nishikawa R, Fujita T, Muranishi S
Department of Biopharmaceutics, Kyoto Pharmaceutical University, Japan.
J Pharm Pharmacol. 1996 Dec;48(12):1285-9. doi: 10.1111/j.2042-7158.1996.tb03937.x.
Sodium glycocholate, sodium taurocholate, sodium deoxycholate, EDTA, sodium salicylate, sodium caprate, diethyl maleate, N-lauryl-beta-D-maltopyranoside, linoleic acid polyoxyethylated (60 mol) mixed micelles (all 20 mM) have been ranked in order of their effectiveness as enhancers of the absorption of drugs in the rat small intestine, by use of an in-situ loop model with phenol red as a model drug. Local toxicity in rats was examined by assessing protein and phospholipid release as biological markers. Of the absorption enhancers, sodium deoxycholate, EDTA and N-lauryl-beta-D-maltopyranoside were the most effective; sodium deoxycholate and EDTA, however, caused significant release of protein and phospholipids. N-lauryl-beta-D-maltopyranoside, on the other hand, did not damage the small intestinal membrane. Sodium taurocholate enhanced phenol red absorption from the small intestine and resulted in little or no protein and phospholipids release. Sodium salicylate, diethyl maleate and the mixed micelles had no absorption-promoting effects on phenol red. There was good correlation between the area under the plasma concentration-time curve for phenol red and the amounts of protein and phospholipid released in the presence of absorption enhancers. From these results it might be concluded that N-lauryl-beta-D-maltopyranoside and sodium taurocholate are effective absorption enhancers which have low toxicity levels at a concentration of 20 mM.
通过使用以酚红为模型药物的原位肠袢模型，对甘氨胆酸钠、牛磺胆酸钠、脱氧胆酸钠、乙二胺四乙酸（EDTA）、水杨酸钠、癸酸钠、马来酸二乙酯、N-月桂酰-β-D-麦芽吡喃糖苷、聚氧乙烯化（60摩尔）亚油酸混合胶束（均为20毫摩尔）在大鼠小肠中作为药物吸收促进剂的有效性进行了排序。通过评估蛋白质和磷脂的释放作为生物学标志物来检测大鼠的局部毒性。在这些吸收促进剂中，脱氧胆酸钠、EDTA和N-月桂酰-β-D-麦芽吡喃糖苷最为有效；然而，脱氧胆酸钠和EDTA会导致蛋白质和磷脂的大量释放。另一方面，N-月桂酰-β-D-麦芽吡喃糖苷不会损伤小肠膜。牛磺胆酸钠可增强小肠对酚红的吸收，且导致蛋白质和磷脂的释放很少或没有释放。水杨酸钠、马来酸二乙酯和混合胶束对酚红没有吸收促进作用。酚红血浆浓度-时间曲线下的面积与吸收促进剂存在时蛋白质和磷脂的释放量之间存在良好的相关性。从这些结果可以得出结论，N-月桂酰-β-D-麦芽吡喃糖苷和牛磺胆酸钠是有效的吸收促进剂，在20毫摩尔的浓度下毒性水平较低。
