EFFECTS OF DIETARY SALT INTAKE ON INTESTINAL CYP3A4 & P GLYCOPROTEIN

膳食盐摄入量对肠道 CYP3A4 的影响

• 批准号: 6297052
• 负责人: KENNETH S LOWN
• 金额: $ 0.02万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6297052
• 关键词: P glycoprotein; clinical research; cytochrome P450; dietary sodium; enzyme activity; gastrointestinal absorption /transport; human subject; isozymes; nutrient intake activity; nutrition related tag; pharmacokinetics

We have shown that the intestinal expression of P-glycoprotein and CYP3A4 and the liver expression of CYP3A4 are able to explain up to 75% of the oral kinetics of some drugs. It was recently reported that low dietary salt intake increased to oral absorption of quinidine, a routinely used antiarrhythmic. Since quinidine is a substrate for both P-glycoprotein and CYP3A4, we hypothesize that the effect of salt is due to changes in the level of expression of P-glycoprotein and/or CYP3A4. This study will directly test this hypothesis by measuring quinidine pharmacokinetics and P-glycoprotein and CYP3A4 levels in subjects placed on low and high salt diets.

我们已经证明，P-糖蛋白和CYP 3A 4的肠道表达以及CYP 3A 4的肝脏表达能够解释某些药物高达75%的口服动力学。最近有报道称，低饮食盐摄入量会增加奎尼丁（一种常用的抗心律失常药物）的口服吸收。由于奎尼丁是P-糖蛋白和CYP 3A 4的底物，我们假设盐的作用是由于P-糖蛋白和/或CYP 3A 4表达水平的变化。本研究将通过测量接受低盐和高盐饮食的受试者中奎尼丁的药代动力学和P-糖蛋白以及CYP 3A 4水平来直接检验这一假设。