Absorption-Enhancing Effect of Nitric Oxide on the Absorption of Hydrophobic Drugs in Rat Duodenum

被引:8
|
作者
Kishimoto, Hisanao [1 ]
Miyazaki, Kaori [1 ]
Takizawa, Yusuke [1 ]
Shirasaka, Yoshiyuki [1 ]
Inoue, Katsuhisa [1 ]
机构
[1] Tokyo Univ Pharm & Life Sci, Sch Pharm, Dept Biopharmaceut, Hachioji, Tokyo 1920392, Japan
关键词
nitric oxide; absorption enhancer; transcellular route; mucus layer; passive diffusion; permeability; duodenum; log P; INTESTINAL EPITHELIAL MONOLAYERS; INDUCED HYPERPERMEABILITY; MEMBRANE; DELIVERY; BARRIER; DONORS; PERMEABILITY; TRANSPORT; MUCUS; MACROMOLECULES;
D O I
10.1002/jps.24677
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Nitric oxide (NO), an endogenous gas that plays a versatile role in the physiological system, has the ability to increase the intestinal absorption of water-soluble compounds through the paracellular route. However, it remains unclear whether NO can enhance the absorption of hydrophobic drugs through the transcellular route. In this study, we examined the absorption-enhancing effect of NO on intestinal permeability of hydrophobic drugs in rat intestine. The pretreatment of rat gastrointestinal sacs with NOC7, a NO-releasing reagent, significantly increased the permeation of griseofulvin from mucosa to serosa in the sacs prepared from the duodenum, but not in those prepared from the other regions such as jejunum, ileum, and colon. The absorption-enhancing effect of NOC7 on the duodenal permeation varied depending on the hydrophobicity of the drugs used. Furthermore, NOC7 treatment was found to be apparently ineffective on the griseofulvin permeation in the duodenum pretreated with dithiothreitol (DTT) that was used as a mucus remover, even though the permeation was increased by pretreatment with DTT alone. These results suggest that NO increases the absorption of hydrophobic drugs through the transcellular route in the duodenum by modulating the mucus layer function. (C) 2016 American Pharmacists Association (R) Published by Elsevier Inc. All rights reserved.
引用
收藏
页码:729 / 733
页数:5
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