Digoxin biotransformation

Abstract

Serum digoxin and metabolites were assayed in plasma and urine by HPLC [high-performance liquid chromatography] in 10 dialysis-dependent patients with end-stage renal failure (group I) and in 5 patients with comparatively normal renal function (group II) after ingestion of 150 .mu.Ci 3H-digoxin-12.alpha.. Thirteen patients were on maintenance digoxin therapy and were at steady state. Metabolites found regularly but usually in small amounts were 3.beta.-digoxigenin and its mono- and bis-digitoxosides, and 3-keto and 3.alpha.(epi)-digoxigenin. Quantitatively the most abundant metabolites were polar and averaged 26% (7-76) of the radioactivity in plasma 6 h after drug, and 60% (11-88) for digoxin for all 15 patients. Neither values between group I and II for the polar metabolites nor digoxin differed significantly. The metabolites reacted with antibody to digoxin to varying degrees and may make up an important component of the serum digoxin concentration when determined by standard radioimmunoassay. In some patients, digoxin undergoes extensive biotransformation apparently by hydrolysis, oxidation, epimerization and conjugation to polar end-metabolites.