Abstract

The rat was more resistant to the lethal properties of all three glycosides (ouabain, digoxin and digitoxin) than either the rabbit or dog. However, the rat's relative resistance was dependent on the glycoside used. The smallest difference in sensitivity was observed with digitoxin in which the rat was 9 times more resistant than the rabbit and 14 times more resistant than the dog; with digoxin, the rat was 25 times more resistant than the rabbit and 92 times more resistant than the dog; the greatest difference was observed with ouabain in which the rat was 63 times more resistant than the rabbit and 110 times more resistant than the dog. Species differences in the biliary excretion of ouabain were reported in a previous study in which it was demonstrated that rats excreted 55% of the drug into bile over a 12-hour period while both rabbits and dogs excreted less than 5%. In the present study, digoxin was excreted into bile similarly by both rats and rabbits (approximately 60% in 12 hours), while dogs excreted only one-fifth that amount. With digitoxin, relatively minor quantitative differences were observed in biliary excretion in the three species studied (45-70% in 12 hours). In all three species, digoxin and digitoxin were excreted against an apparent bile to plasma concentration gradient, ranging from 10 to 300. These data suggest that 1) digoxin and digitoxin are excreted into the bile by a transport process, 2) no general correlation between the polarity of cardiac glycosides and their biliary excretion exists and 3) the additional resistance of the rat to the lethal properties of ouabain and digoxin over that. observed with digitoxin appears to be partially due to a higher rate of excretion of these two glycosides into the bile.