Phenobarbital-digitoxin interaction in the guinea pig liver

The influence of phenobarbital pretreatment on liver concentration of digitoxin and its metabolites was studied in guinea-pigs after i.p. administration of the cardiac glycoside. During the first hour an increase in liver uptake was observed in pretreated animals. The differences detected in the hepatic subcellular distribution do not seem to explain the higher concentrations found in the liver of phenobarbital pretreated animals. About 80% of the liver radioactivity was found in the supernatants. Inhibition of digitoxin biotransformation by phenobarbital was demonstrated by chromatographic analysis of the organic soluble compounds present in the supernatants. The possible binding of digitoxin and its metabolites to soluble proteins of liver cytosol was excluded by thin-layer gel filtration. The decrease in digitoxin biotransformation seems to be the reason for the increase in liver uptake and for the decrease in bile concentrations, observed in phenobarbital pretreated animals.