Biliary Excretion of Iopanoic Acid in Gunn Rats 1

Abstract

Abstract

Patients 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 that there is no difference in the hepatic disposition of IOP in the Gunn rat compared to the normal, despite the inability of the former to conjugate bilirubin.