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Studies on digitalis; XII. Kinetic pattern of digitoxin metabolism in patients with biliary fistulas
Author(s) -
Storstein Liv,
Amlie Jan
Publication year - 1977
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt1977216659
Subject(s) - digitoxin , enterohepatic circulation , urine , chemistry , hydroxylation , metabolism , metabolite , digitalis , chromatography , hydrolysis , medicine , biochemistry , enzyme , digoxin , heart failure
The metabolic pattern of cardioactive and inactive, conjugated metabolites (a maximum of 24 substances) was studied after a single intravenous dose of 0.6 mg digitoxin in two female patients (aged 72 and 62 yr) with biliary fistulas. Bile and urine were collected every twenty‐fourth hour and the 1‐, 2‐, 4‐, 6‐, and 8‐day samples were analyzed. With the methods used, enzymatic cleavage of conjugation bonds, TLC (thin‐layer chromatography), and a modified 86 Rb method, the products of hydroxylation, hydrolysis, and conjugation could be separated. All cardioactive metabolites were present in bile and all were conjugated. Unchanged digitoxin was the main substance excreted. Hydrolyzed and conjugated metabolites formed a greater part of the substances excreted in bile than hydroxylated metabolites. The metabolic pattern in bile did not change much with time. The metabolic pattern in urine showed no close resemblance to that in bile. Hydroxylated, hydrolyzed, and conjugated metabolites were equally predominant in urine. Interruption of the enterohepatic circulation by T tube drainage not only changed the elimination kinetics of digitoxin 18 but also changed the pattern of digitoxin metabolites in urine.