Absorption process of salazosulfapyridine in human intestinal epithelial cells and rat intestine
Kazumasa Naruhashi*, Akiko Kamino, Ena Ochi, Erina Kusabiraki, Megumi Ueda, Shinichi Sugiura, Hirokazu Nakanishi and Nobuhito Shibata
Faculty of Pharmaceutical Sciences, Doshisha Women’s College of Liberal Arts, Kyoto, Japan
- *Corresponding Author:
- Kazumasa Naruhashi
Faculty of Pharmaceutical Sciences
Doshisha Women’s College of Liberal Arts
Kodo Kyotanabe-shi, Kyoto 610-0395, Japan
E-mail: [email protected]
Received date: September 14, 2016; Accepted date: September 23, 2016; Published date: September 28, 2016
Citation: Naruhashi K, Kamino A, Ochi E, Kusabiraki E, Ueda M, et al. (2016) Absorption Process of Salazosulfapyridine in Human Intestinal Epithelial Cells and Rat Intestine. Clin Pharmacol Biopharm 5:165. doi:10.4172/2167-065X.1000165
Copyright: © 2016 Naruhashi K, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Introduction: Salazosulfapyridine (SASP) is an oral medication used to treat rheumatoid arthritis and inflammatory bowel disease, particularly ulcerative colitis. It has been reported that various transporters such as P-glycoprotein (Pgp) and multidrug resistance-associated protein 2 (MRP2), are involved in the transport of SASP. P-gp and MRP2 are expressed in the brain, intestine, and various tissues in both humans and rats. In the intestine, P-gp limits the absorption of certain drugs, however, its mode of absorptive action with regard to SASP has not, as of yet been studied. The aim of this study was to investigate the intestinal transport of SASP and examine whether transporters such as P-gp and MRP2 are involved in this process.
Method: Bidirectional permeability and inhibition transport studies were performed using Caco-2 and T84 cell lines. Transcellular transport studies were conducted using isolated rat intestinal tissue mounted in an Ussing-type chamber. The intestinal absorption was examined using an in-situ closed-loop experiment in rats.
Results: SASP showed secretory-directed transport across Caco-2 and T84 cells, as well as rat intestinal tissue. Cyclosporine A (CsA), a P-gp inhibitor, was found to decrease this secretory-directed transport. In the intestinal closedloop experiment, addition of CsA resulted in increased accumulation of SASP; however, this was too miniscule to be considered. The inhibition study showed that both secretory and absorptive transporters sensitive to probenecid are involved in the process of SASP absorption in the small intestine.
Conclusion: In the process of SASP absorption in the intestine, CsA-sensitive secretory transporters including P-gp as well as probenecid-sensitive absorptive and secretory-transporters are involved and the total of the absorption of SASP is regulated by these transporters. It is likely that these transporters are coordinated in a complex manner to effectively regulate absorption of SASP and other biochemically similar drugs.