Enhanced transformation of digitoxin to dihydrodigitoxin in humans with renal failure

A gas-chromatographic mass-spectroscopic technique was used to identify dihydrodigitoxin, a metabolite of digitoxin, in the plasma of healthy volunteers and patients with renal failure. Digitoxin and dihydrodigitoxin were extracted from plasma and derivatized with heptafluorbutyric anhydride. In normal subjects, only minimal concentrations of dihydrodigitoxin in plasma could be determined (1 ng/ml) after an intravenous bolus injection of digitoxin. Under a chronic treatment with a daily dose of 0.1 mg digitoxin in three out of seven individuals, detectable dihydrodigitoxin plasma levels were observed (0.7, 1.5, and 1.7 ng/ml) (Table I). On the other hand, in seven patients with renal failure, high dihydrodigitoxin plasma concentrations (8.9 +/- 0.9 ng/ml) were shown which were in a similar range as those of the parent compound (8.7 +/- 2.2 ng/ml) under a maintenance treatment with digitoxin.