Active Secretion of Drugs from the Small Intestinal Epithelium in Rats by P-Glycoprotein Functioning as an Absorption Barrier

• DOI: 10.1111/j.2042-7158.1996.tb05904.x
• Publication Date: 2011-04-13T11:04:55Z
• Authors: Toshimitsu Terao; Etsuko Hisanaga; Yoshimichi Sai; Ikumi Tamai; Akira Tsuji
• Keywords: P-glycoprotein; Nadolol; Acebutolol; Paracellular transport

Abstract Because the significance of P-glycoprotein in in-vivo secretion β-blockers intestinal epithelial cells is unclear, secretory mechanism for and other drugs has been evaluated. Uptake acebutolol, celiprolol, nadolol timolol, antiarrhythmic agent, quinidine by multidrug-resistant leukaemic cell line variant K562/ADM was significantly lower than that drug-sensitive K562 cells, suggesting these are transported out cells. The reduced uptake acebutolol drug-resistant reversed treating with anti-P-glycoprotein monoclonal antibody, MRK16, whereas no such alteration observed Acebutolol was, moreover, markedly enhanced, a concentration-dependent manner, presence specific inhibitors, MS-209 cyclosporin. Caco-2 were used evaluation role permeability to in-vitro. Basolateral-to-apical transport twice reverse direction. A similar polarized flux also vinblastine, but not acetamide or mannitol. When absorption evaluated rat jejunal loop method, simultaneous intravenous administration inhibitor, cyclosporin, both vinblastine increased 2.6- 2.2-fold, respectively, enhancement acetamide. effect cyclosporin on several further examined, extent contribution as an barrier those ATP depletion occlusion superior mesenteric artery resulted clear increase 3-O-methylglucose acetamide, indicating secreted ATP-dependent into lumen. These findings demonstrate plays transporting from