title: Effects of 2 Polyoxyethylene Alkyl Ethers on the Function of Intestinal P-glycoprotein and Their Inhibitory Mechanisms.
abstract: The purpose of this study was to investigate the effects of polyoxyethylene 10-oleyl ether and polyoxyethylene 9-lauryl ether, 2 polyoxyethylene alkyl ethers, on the transport and absorption of 2 P-glycoprotein (P-gp) substrates, quinidine and prednisolone, across the intestinal membrane and to elucidate the inhibitory mechanisms of intestinal P-gp by these polyoxyethylene alkyl ethers. For in vitro studies, we used a diffusion chamber method and the Caco-2 cell model. An in situ closed-loop method was used for in vivo study. The 2 polyoxyethylene alkyl ethers, nonionic surfactants, increased the intestinal absorptive transport of quinidine and prednisolone in the diffusion chamber studies, and absorptive permeability was enhanced in the in vitro Caco-2 cell study. Furthermore, these surfactants enhanced the rat intestinal absorption of prednisolone, and we observed no intestinal membrane damage in the presence of these surfactants. Furthermore, these surfactants increased membrane fluidity in intestinal brush border membranes and inhibited P-gp ATPase activity. For in vitro and in vivo studies, these surfactants enhanced the intestinal absorption of quinidine and prednisolone, 2 P-gp substrates. The alteration in intestinal membrane fluidity and the inhibition of P-gp ATPase activity by these 2 polyoxyethylene alkyl ethers may be confirmed as mechanisms of P-gp inhibition.
authors: Department of Biopharmaceutics, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
authors: Wanting
authors: W
authors: Zhao
authors: Department of Biopharmaceutics, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
authors: Tammam
authors: T
authors: Alama
authors: Department of Biopharmaceutics, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
authors: Kosuke
authors: K
authors: Kusamori
authors: Department of Biopharmaceutics, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
authors: Hidemasa
authors: H
authors: Katsumi
authors: Department of Biopharmaceutics, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
authors: Toshiyasu
authors: T
authors: Sakane
authors: Department of Biopharmaceutics, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan. Electronic address: yamamoto@mb.kyoto-phu.ac.jp.
authors: Akira
authors: A
authors: Yamamoto
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000818:Animals; D018938:Caco-2 Cells; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009924:Organ Culture Techniques; D000077423:Polidocanol; D011092:Polyethylene Glycols / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; C478746:polyoxyethylene-10-oleyl ether; D000077423:Polidocanol; D011092:Polyethylene Glycols
keywords: ATPase activity; P-glycoprotein; intestinal absorption; membrane fluidity; polyoxyethylene alkyl ethers