Biliary Excretion of Iopanoic Acid in Gunn Rats

Abstract

AbstractPatients with the Crigler-Najjar syndrome lack hepatic microsomal UDP-glucuronyl transferase activity which is necessary for conjugating bilirubin with glucuronic acid. The gallbladder of these patients opacify normally on oral cholecystography with iopanoic acid (IOP), a contrast agent which like bilirubin, is conjugated with glucuronic acid prior to transport into bile. Experiments were performed with normal (Sprague-Dawley) and Gunn rats (a strain which lacks UDP-glucuronyl transferase activity) to determine the effect of this enzyme deficiency on the hepatic disposition of IOP. Bilirubin excretion in Gunn rats was less than 1% of the Sprague-Dawley animals, while IOP excretion in bile was not statistically different between the two strains whether the contrast agent was infused as IOP or as IOP-glucuronide. HPLC analysis showed that IOP distribution in Gunn rat bile was 92% IOP-G and 8% IOP. The hepatic intracellular distribution of IOP was the same in the two strains. The results indicate tha...