Increased Bilirubin Conjugation in Heterozygous Gunn Rats treated with Phenobarbital

Abstract

THE mechanism by which phenobarbital lowers serum bilirubin levels in some patients with jaundice is undefined^1–3 although there is some evidence of enhanced synthesis of bilirubin glucuronyl transferase^4–7, the hepatic microsomal enzyme which mediates the conjugation of bilirubin before it is excreted into bile. It is also possible, however, that phenobarbital acts by augmenting other excretory pathways involving the degradation of bilirubin to polar breakdown products^1–3,8. If phenobarbital enhances the capacity of the liver to conjugate bilirubin, response to drug therapy should be associated with increased excretion of bilirubin into bile. If, on the other hand, phenobarbital augments the other excretory pathways, bile bilirubin should remain unchanged. I have investigated this in male heterozygous and homozygous Gunn rats and Sprague–Dawley rats, weighing 350–500 g.