Different Effects of Microsomal Enzyme Inducers on the Biliary Excretion of Digoxin1

Abstract The effects of pretreatment with spironolactone, phenobarbital and 3,4–benzpyrene on biliary excretion of digoxin was studied in the isolated perfused rat liver system after a single dose of ³H–digoxin. After spironolactone pretreatment (100 mg/kg intraperitoneally for 4 days) the treated group excreted into bile in 45 min. 67 % of the administered dose compared to about 27 % in the control group. Since there was no significant increase in bile flow at any of the time periods, the enhanced biliary excretion of digoxin was entirely due to the increase in the bile level of digoxin or its metabolites or both. Pretreatment with phenobarbital (75 mg/kg intraperitoneally for 4 days) resulted in a slight increase in bile level of tritium at 15 min. and in bile flow, which could account for the doubled amount of digoxin excreted by the treated group, as compared to the control group at 45 min. Bile flow and biliary excretion of digoxin were unaffected by pretreatment with 3,4–benzpyrene (20 mg/kg intraperitoneally for 4 days). The results suggest that the enhancing effect of spironolactone and phenobarbital on biliary excretion of digoxin is a result of different mechanisms of action, which can not be directly related to the induction of microsomal drug metabolism.