Excretion patterns of 125I-radioiodohippuric acid in normal and in chronically uremic rats

Chronic uremia was induced in male Wistar rats by sequential sub-total and contralateral nephrectomies, followed by long term maintenance after surgery. 4-[ 125I]-Iodohippuric acid, 3,5-di[ 125I]-iodohippuric acid and 3,4,5-tri[ 125I]-iodohippuric acid were synthesized, and injected individually into the femoral veins of normal and uremic rats. Non-invasive measurements of blood hepatic and renal radioactivity levels in anesthetized animals were obtained by external gamma scintillation probes, and biliary excretion was measured following cannulation of the common bile duct. The expected pattern of increased biliary elimination with increased molecular weight was found to be accentuated in the uremic model. The importance of this hepatic compensation in chronic uremia is discussed with respect to xenobiotic clearance as part of a therapeutic regimen. Plasma clearance, hepatic and renal uptake, and biliary elimination data are given for each of the three.