萨拉唑磺胺吡啶在人肠上皮细胞和大鼠肠中的吸收过程

K. Naruhashi, Akiko Kamino, E. Ochi, Erina Kusabiraki, M. Ueda, S. Sugiura, Hirokazu Nakanishi, N. Shibata
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引用次数: 1

摘要

简介:Salazosulfapyridine (SASP)是一种用于治疗类风湿性关节炎和炎症性肠病,特别是溃疡性结肠炎的口服药物。据报道,多种转运蛋白如p -糖蛋白(Pgp)和多药耐药相关蛋白2 (MRP2)参与了SASP的转运。P-gp和MRP2在人类和大鼠的大脑、肠道和各种组织中都有表达。在肠道中,P-gp限制了某些药物的吸收,然而,其对SASP的吸收作用模式尚未被研究。本研究的目的是研究SASP的肠道转运,并检查P-gp和MRP2等转运蛋白是否参与这一过程。方法:用Caco-2和T84细胞株进行双向通透性和抑制转运研究。跨细胞转运研究使用分离的大鼠肠组织安装在ussing型室。采用原位闭环实验法检测大鼠肠道吸收。结果:SASP在Caco-2和T84细胞以及大鼠肠组织中表现出分泌导向转运。环孢素A (CsA),一种P-gp抑制剂,被发现可以减少这种分泌导向的运输。在肠闭环实验中,添加CsA导致SASP积累增加;然而,这是微不足道的考虑。抑制研究表明,小肠中对probenecid敏感的分泌转运体和吸收转运体都参与了SASP的吸收过程。结论:SASP在肠内吸收过程中,包括P-gp在内的csa敏感的分泌转运蛋白以及probenide敏感的吸收转运蛋白和分泌转运蛋白参与其中,SASP的吸收总量受这些转运蛋白的调控。这些转运体可能以复杂的方式协调,有效地调节SASP和其他生化类似药物的吸收。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Absorption process of salazosulfapyridine in human intestinal epithelial cells and rat intestine
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.
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