EXCRETION OF ³H-DIGITOXIN AND ITS METABOLITES FOLLOWING SPIRONOLACTONE PRETREATMENT IN RATS

¹ Department of Pharmacology and Toxicology, School of Pharmacy, University of Kansas

Spironolactone pretreatment of male rats caused a marked decrease in the urinary excretion of digitoxin and its metabolites. Focal excretion of these compounds was markedly increased in treated animals. The net effect of these changes was increased elimination of digitoxin-related compounds. The greatest changes in urinary excretion occurred with hydroxylation products of digitoxin (i.e., digoxin-related compounds). which were decreased in spironolactone-pretreated animals. The most striking change in the fecal excretion of digitoxin metabolites occurred with the monodigitoxoside of digitoxin. The amount of this metabolite in the feces of spironolactone-pretreated animals was over 100 times greater than that recovered from the feces of control animals. These results suggest that the protective effect of spironolactone on digitoxin toxicity is not the result of increased urinary excretion of digitoxin or its metabolites. but is apparently related to enhanced fecal excretion of digitoxin metabolites.