ROLE OF P GLYCOPROTEIN IN CATIONIC RENAL TUBULAR SECRETION

这项研究的使命是开发量化肾小球和肾小管功能的方法。 一旦建立，我们希望使用这些工具来评估年龄，性别和各种疾病过程，如糖尿病肾病，高血压，肾小球肾炎，肝硬化和艾滋病毒对肾功能的影响。 本研究项目的目的是检验p-糖蛋白转运是法莫替丁肾小管排泄的主要成分这一假设。 这将在一项随机化研究中完成，该研究涉及在肾功能正常的健康志愿者中单独静脉给予西咪替丁和法莫替丁以及与口服伊曲康唑联合给药。 西咪替丁和法莫替丁都通过阳离子途径进行广泛的肾小管分泌。 体外研究表明，西咪替丁通过p-糖蛋白转运从肾小管细胞转运到尿液中。 因此，在此将其用作阳性对照;存在伊曲康唑（一种有效的体外P-糖蛋白抑制剂）时，其肾脏排泄应减少。 在每项研究中，将使用广泛接受的连续碘酞酸盐和PAH肾脏清除率方法监测肾小球滤过率（GFR）、有效肾血浆流量（ERPF）和滤过分数（FF）。 将使用尿排泄率和GFR计算西咪替丁和法莫替丁单独给药和与伊曲康唑联合给药时的肾小管分泌率。

The research mission is to develop methodologies to quantify glomerular and tubular function. Once established, we hope to use these tools to assess the influence of aging, gender and various disease processes such as diabetic nephropathy, hypertension, glomerulonephritis, hepatic cirrhosis and HIV on renal function. The aim of this research project is to test the hypothesis that p-glycoprotein transport is a major component of the renal tubular excretion of famotidine. This will be accomplished in a randomized study involving administration of intravenous cimetidine and famotidine alone and in combination with oral itraconazole to healthy volunteers with normal renal function. Both cimetidine and famotidine undergo extensive tubular secretion by cationic pathway. In vitro studies suggest that cimetidine is transported from renal tubular cells into the urine by p-glycoprotein transport. Thus, it will be utilized here as a positive control; its renal excretion should decrease in the presence of itraconazole, a potent in vitro inhibitor of p-glycoprotein. Glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and filtration fraction (FF) will be monitored throughout each study using the widely accepted method of continuous iothalamate and PAH renal clearances. The urinary excretion rate and GFR will be used to calculate the rate of tubular secretion of cimetidine and famotidine when given alone and in the presence of itraconazole.