digitoxin and Cholelithiasis

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 86Rb 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 but also changed the pattern of digitoxin metabolites in urine.

Topics: Adult; Aged; Bile; Biliary Fistula; Cholecystectomy; Cholelithiasis; Clinical Trials as Topic; Digitoxin; Enterohepatic Circulation; Female; Humans; Hydrolysis; Hydroxylation; Male; Middle Aged

Simultaneous serum, urine, and bile measurements of digitoxin and its cardioactive metabolites were preformed in 5 cholecystectomized patients with T tube drainage. A 86Rb method was used for serum and urine analysis. The recovery of digitoxin and cardioactive metabolites in two extractions with dichloromethane was 93%; 7% was left in bile. Peak bile concentrations had a mean value of 41.6 ng/ml and were seen after 15 to 60 min. Bile concentration was higher than serum and urine concentration after 24 hr. Mean T/2 of serum elimination was 4.3 days and 8.1 days in 5 control subjects (p less than 0.01). Mean urine concentration T/2 was 10.4 days and 7.2 days in the control subjects (not significant). Mean bile concentration T/2 was 3.5 days. Urinary excretion of digitoxin and cardioactive metabolites was the same in the two groups. The biliary fistula group excreted 22.5% in urine and bile of a dose after 8 days, whereas it was 15.8% in the control subjects. The ratio between the cumulative excretion in urine and bile varied between 1.6 and 2.2. These findings demonstrate that direct interruption of the enterohepatic circulation leads to a marked reduction in serum half-time of digitoxin and cardioactive metabolites, but T/2 is still longer than for other glycosides, indicating that factors other than the enterohepatic circulation are of importance in the slow elimination of digitoxin.

Topics: Adult; Aged; Bile; Biliary Fistula; Cholecystectomy; Cholelithiasis; Digitoxin; Female; Half-Life; Humans; Kinetics; Liver Circulation; Male; Methods; Middle Aged; Radioisotopes; Rubidium

Topics: Adrenal Gland Diseases; Adult; Arrhythmias, Cardiac; Athletic Injuries; Autopsy; Cardiomegaly; Cholelithiasis; Coronary Vessel Anomalies; Coronary Vessels; Death, Sudden; Digitalis; Electrocardiography; Heart Conduction System; Heart Diseases; Humans; Male; Military Medicine; Myocarditis; Myocardium; Phytotherapy; Plants, Medicinal; Plants, Toxic; Pulmonary Edema; Quinidine; Thymus Gland