Dihydrodigitoxin, a Metabolite of Digitoxin in Humans

Digitalis in Chronic Renal Insufficiency

“…Increased extrarenal clearance of digitoxin in renal failure is apparently not the result of increased hepatobiliary clearance, but due to increased intestinal secretion [62], In contrast to previous reports [63], 12-betahydroxylation of digitoxin to digoxin does not occur to a major extent in uremic patients [51]. There is still some controversy as to the actual scrum concentrations of the relatively bioinactive metabolite dihydrodigitoxin in uremic patients [64], Because of unchanged total body clearance, steady-state plasma concentrations of digitoxin are not increased when patients with renal insufficiency are given normal loading and maintenance doses.…”

Reductive inactivation of digitoxin by Eubacterium lentum cultures

“…In summary, cultures of E. lentum reduced DT3 and its sugar-hydrolyzed metabolites to the corresponding 20Rdihydro derivatives. As previously discussed for DG3, this reduction reaction may contribute significantly to the inactivation of DT3 in some patients (2,9,10,18).…”

“…Whereas it was previously thought that DT3 and DG3 escape extensive metabolic degradation in humans, it is now recognized that the metabolism of these drugs may be significant in some patients (6,9,12,14,16). Reduction of the double bond in the lactone ring of DT3 and DG3 leads to the formation of the corresponding dihydro compounds (2,23). Recent studies have suggested that more than one-third of the patients taking DG3 excrete detectable quantities of reduced metabolites in the urine.…”