title: Absorption-Enhancing Effect of Nitric Oxide on the Absorption of Hydrophobic Drugs in Rat Duodenum.
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.affiliation: Department of Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Hisanao
authors.initials: H
authors.lastname: Kishimoto
authors.affiliation: Department of Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Miyazaki
authors.affiliation: Department of Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Takizawa
authors.affiliation: Department of Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Shirasaka
authors.affiliation: Department of Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan. Electronic address: kinoue@toyaku.ac.jp.
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Inoue
mesh_terms: D000818:Animals; D004357:Drug Synergism; D004386:Duodenum / Q000187:drug effects* / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions / Q000187:drug effects*; D007408:Intestinal Absorption / Q000187:drug effects* / Q000502:physiology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014226:Triazenes / Q000008:administration & dosage / Q000378:metabolism
chemical_list: C100973:(1-hydroxy-2-oxo-3-(N-methyl-3-aminopropyl)-3-methyl-3-aminopropyl)-3-methyl-1-triazene; D014226:Triazenes; D009569:Nitric Oxide
keywords: absorption enhancer; duodenum; log P; mucus layer; nitric oxide; passive diffusion; permeability; transcellular route