Metabolism and cardiac actions of a polar aminocardenolide and digoxin in the conscious dog

We studied the metabolism and cardiac actions of a polar aminocardenolide, 3-β-O-(4-amino-4,6-dideoxy-β-D-galactopyranosyl) digitoxigenin (ASI-222), in conscious, chronically instrumented dogs and compared the cardiac actions of this compound with those of digoxin. Chloroform-soluble metabolites and the excretion patterns of ASI-222 in urine and feces were identified and measured using thin-layer chromatography. The deaminated metabolites of ASI-222 appeared both in the urine and the feces together with the genin, digitoxigenin and the parent drug which constituted the majority of the radioactivity excreted. There was a secondary rise in the plasma concentration of ASI-222 starting 2 hr after the i.v. administration, which strongly suggests its enterohepatic recycling. The secondary increase in the plasma concentration was not seen in the dogs receiving digoxin. ASI-222 produced increases in cardiac contractility and systolic blood pressure which were more rapid in onset and shorter in duration than those produced by an equimolar dose of digoxin. Amplitudes of these physiologic responses to these two compounds in conscious dogs were approximately 2 times higher than the effects previously reported to similar doses in anesthetized dogs.