title: Effect of proinflammatory cytokine IL-6 on efflux transport of rebamipide in Caco-2 cells.
abstract: 1. Effect of IL-6, a pro-inflammatory cytokine, on efflux transport of rebamipide, an antiulcer drug, was investigated in Caco-2 cells. 2. Rebamipide had a greater basal-to-apical than apical-to-basal transport rate. Efflux transport of rebamipide was inhibited by cyclosporine A, a P-gp inhibitor, and probenecid, which is a general MRP inhibitor, but not by Ko143, a BCRP inhibitor. 3. By the addition of IL-6, mannitol transport was slightly increased in a concentration-dependent manner in both directions of absorption and efflux. The addition of IL-6 did not change efflux transport of rebamipide even though efflux transport of digoxin, a typical substrate of P-gp, was significantly decreased by the addition of IL-6, indicating decrease of the function of P-gp. 4. Therefore, it was suggested that increase of MRP(s)-mediated transport compensates for the decrease of P-gp mediated transport of rebamipide. These findings suggested that rebamipide absorption is unlikely to be changed in IBD patients.
authors.affiliation: a Drug Delivery Research, Department of Pharmacy, Uppsala University , Uppsala , Sweden and.|b Bioavailability Research Project, Formulation Research Institute, Otsuka Pharmaceutical Co. Ltd , Tokushima , Japan.
authors.forename: Masateru
authors.initials: M
authors.lastname: Miyake
authors.affiliation: a Drug Delivery Research, Department of Pharmacy, Uppsala University , Uppsala , Sweden and.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nakai
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000378:metabolism; D000897:Anti-Ulcer Agents / Q000378:metabolism*; D018938:Caco-2 Cells; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D015363:Quinolones / Q000378:metabolism*
chemical_list: D000897:Anti-Ulcer Agents; D015850:Interleukin-6; D015363:Quinolones; C052785:rebamipide; D000409:Alanine
keywords: Caco-2 cells; IL-6; efflux transporters; intestinal drug absorption; permeability; rebamipide