Tags

Type your tag names separated by a space and hit enter

Absorption-Enhancing Effect of Nitric Oxide on the Absorption of Hydrophobic Drugs in Rat Duodenum.
J Pharm Sci. 2016 Feb; 105(2):729-733.JP

Abstract

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.

Authors+Show Affiliations

Department of Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.Department of Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.Department of Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.Department of Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.Department of Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan. Electronic address: kinoue@toyaku.ac.jp.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26458075

Citation

Kishimoto, Hisanao, et al. "Absorption-Enhancing Effect of Nitric Oxide On the Absorption of Hydrophobic Drugs in Rat Duodenum." Journal of Pharmaceutical Sciences, vol. 105, no. 2, 2016, pp. 729-733.
Kishimoto H, Miyazaki K, Takizawa Y, et al. Absorption-Enhancing Effect of Nitric Oxide on the Absorption of Hydrophobic Drugs in Rat Duodenum. J Pharm Sci. 2016;105(2):729-733.
Kishimoto, H., Miyazaki, K., Takizawa, Y., Shirasaka, Y., & Inoue, K. (2016). Absorption-Enhancing Effect of Nitric Oxide on the Absorption of Hydrophobic Drugs in Rat Duodenum. Journal of Pharmaceutical Sciences, 105(2), 729-733. https://doi.org/10.1002/jps.24677
Kishimoto H, et al. Absorption-Enhancing Effect of Nitric Oxide On the Absorption of Hydrophobic Drugs in Rat Duodenum. J Pharm Sci. 2016;105(2):729-733. PubMed PMID: 26458075.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Absorption-Enhancing Effect of Nitric Oxide on the Absorption of Hydrophobic Drugs in Rat Duodenum. AU - Kishimoto,Hisanao, AU - Miyazaki,Kaori, AU - Takizawa,Yusuke, AU - Shirasaka,Yoshiyuki, AU - Inoue,Katsuhisa, Y1 - 2016/01/11/ PY - 2015/07/17/received PY - 2015/09/04/revised PY - 2015/09/16/accepted PY - 2015/10/13/entrez PY - 2015/10/13/pubmed PY - 2016/12/15/medline KW - absorption enhancer KW - duodenum KW - log P KW - mucus layer KW - nitric oxide KW - passive diffusion KW - permeability KW - transcellular route SP - 729 EP - 733 JF - Journal of pharmaceutical sciences JO - J Pharm Sci VL - 105 IS - 2 N2 - 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. SN - 1520-6017 UR - https://www.unboundmedicine.com/medline/citation/26458075/Absorption_Enhancing_Effect_of_Nitric_Oxide_on_the_Absorption_of_Hydrophobic_Drugs_in_Rat_Duodenum_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-3549(15)00097-0 DB - PRIME DP - Unbound Medicine ER -