Relevant metabolism of cardiac glycosides

Summary

With regard to the metabolism of digitalis glycosides, recent experiments show that cleavage of the sugar residues in the liver is not simple hydrolysis but an oxidative process which is catalyzed by the cytochrome P 450 system.

The enzymatic 12 β-hydroxylation of digitoxin to digoxin is quantitatively neglisible in man.

The pattern of digitoxin and digoxin metabolites, which is found to be fairly inhomogeneous in various studies, considerably depends on the different experimental designs, for instance, on the mode of administration. The relatively low recovery of the glycosides and their metabolites in urine and (if investigated) also in feces makes the evaluation of metabolism and its magnitude more difficult. Approximately, digitoxin is metabolized to 20–50%, digoxin to 5–50%.

With respect to strophanthus glycosides, an insufficient recovery was also noted in most of the studies. In contrast to ouabain, cymarin and orally given k-strophanthoside were found to be highly metabolized in urine. Intravenously injected k-strophanthoside was excreted in urine mainly as unchanged drug.