title: Arbekacin is actively secreted in the rat intestine via a different efflux system from P-glycoprotein.
abstract: This study was undertaken to examine the secretory transport of arbekacin, an aminoglycoside antibiotic, in the rat small intestine and to compare it with those in Caco-2 and LLC-PK1 cells. In vitro permeation of arbekacin was examined using an Ussing chamber technique. Serosal-to-mucosal (secretory)/mucosal-to-serosal (absorptive) permeation ratios of 0.5 mM arbekacin were 2.8 in the jejunum and 7.0 in the ileum, respectively, indicating that arbekacin permeation was highly secretory-oriented. In the ileum, the ratios became smaller with increase in arbekacin concentration applied. When D-glucose was replaced with 3-o-methyl-D-glucose in the experimental medium, the directionality of the arbekacin permeation disappeared almost completely. Absorptive permeation of arbekacin was not significantly influenced by verapamil, cyclosporin A, or probenecid. On the other hand, when gentamicin sulfate was added to the serosal medium, secretory transport of arbekacin was significantly inhibited. The results of this study strongly suggest that a specialized efflux system other than P-glycoprotein and multidrug resistance proteins was involved in the secretory transport of arbekacin in the rat intestine. There was no directionality in arbekacin permeation across Caco-2 cell monolayers, suggesting the absence or very slight expression of the secretory system for arbekacin in this cell line.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido 061-0293, Japan. saitoh@hoku-iryo-u.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saitoh
authors.forename: Yuji
authors.initials: Y
authors.lastname: Arashiki
authors.forename: Ayako
authors.initials: A
authors.lastname: Oka
authors.forename: Masako
authors.initials: M
authors.lastname: Oda
authors.forename: Yuko
authors.initials: Y
authors.lastname: Hatakeyama
authors.forename: Michiya
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Kaoru
authors.initials: K
authors.lastname: Hosoi
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000617:Aminoglycosides / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D018938:Caco-2 Cells; D003982:Dibekacin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013552:Swine
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000617:Aminoglycosides; D003982:Dibekacin; C031986:arbekacin