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Studies on digitalis; II. The influence of impaired renal function on the renal excretion of digitoxin and its cardioactive metabolites

Simultaneous serum and urine measurements of digitoxin and its cardioactive metabolites were performed in patients with impaired renal function, after a single dose and during maintenance therapy. A modified 86Rb method was used. Comparison of serum levels after intravenous and peroral dosage of digitoxin in 5 patients with severe uremia showed that absorption was complete. After an intravenous dose, the serum‐tissue eqUilibration T/2 in renal failure had a mean value of 150 minutes, while it was 71 minutes in the control subjects. Mean T/2 of serum elimination was 3.9 days and 8.1 days in 5 control subjects (p < 0.01). The urine digitoxin concentration T/2 with a mean value of 8.0 days did not differ significantly from the control subjects (7.2 days). The urine levels were, however, lower in uremics with lower cumulative excretion during an 8 day period. Eleven patients with slightly impaired renal function (creatinine clearance 50 to 80 ml per minute) on maintenance dosage did not differ Significantly from a control group of 22 patients. Twelve patients with uremia (mean serum creatinine 12.2 mg per 100 ml) had serum levels in the same range as the control subjects, but significantly lower urine levels, renal excretion, and digitoxin clearance. They excreted 13.6% of the daily dose compared to the 32.9% of the controls. The results indicate that compensatory mechanisms are operative in uremia as increased excretion through other pathways or as changes in hepatic metabolism of digitoxin.