EFFECTS OF DIETARY SALT INTAKE ON INTESTINAL CYP3A4 & P GLYCOPROTEIN

我们发现P-糖蛋白和细胞色素P3A4在肠道的表达以及肝脏细胞色素P3A4的表达可以解释高达75%的某些药物的口服动力学。最近有报道称，饮食盐摄入量低会增加奎尼丁的口服吸收，奎尼丁是一种常规使用的抗心律失常药物。由于奎尼丁是P-糖蛋白和CYP3A4的底物，我们假设盐的作用是由于P-糖蛋白和/或CYP3A4表达水平的变化。这项研究将通过测量低盐饮食和高盐饮食受试者的奎尼丁药代动力学以及P-糖蛋白和细胞色素P3A4水平来直接验证这一假说。

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 hypothesize by measuring quinidine pharmacokinetics and P-glycoprotein and CYP3A4 levels in subjects placed on low and high salt diets.