Alternative transport pathways of cholephilic 14C-hexobarbital metabolites in rats with experimental hepatitis and cholestasis.

Abstract

Object of the investigation was to find out whether otherwise cholephilic metabolites are excreted via an alternative pathway into urine in experimental liver disease. Intraduodenal application of 14C-labelled hexobarbital in rats is followed by an immediate biliary excretion of metabolites in the range of 400 microgram/100 g bw/h. Using TLC these metabolites can be separated into a polar fraction (about 80% of total) and a non-polar fraction. Phenobarbital treatment leads to a decrease of the total biliary excretion of metabolites to about 200 microgram/100 g bw/h, the metabolite pattern remaining unchanged. Animals with a mild form of GalN-hepatitis had a moderate reduction of bile flow and a total metabolite output of 40 microgram/100/gbw/h. The metabolite pattern showed a decrease mainly of the polar fraction. In animals with an early stage of ANIT cholestasis a 50% reduction of bile flow was associated with a total metabolite excretion of only 20 microgram/100 g bw/h and polar metabolites were nearly absent. In both types of experimental liver disease in corresponding urine samples otherwise cholephilic metabolites appeared. The results obtained show that clinically moderate stages of experimental liver disease lead to a significantly diminished output especially of polar 14C-hexobarbital-metabolites into the bile, which can, therefore, appear in the urine instead.