Formation and disposition of bis- and monoglycosides after administration of³H-4‴-methyldigoxin to man

Summary

The metabolites of tritiated 4‴-methyldigoxin (MD) has been studied in bile, urine and faeces from 3 patients 24 h after cholecystectomy and T-tube drainage. 5.6–15.6% of the doses were eliminated in bile and 28.5–57.8% in urine within 48 h. In bile after 6 h, approximately 5% of the excreted products were bisglycosides (B) and only traces were monoglycosides (M), whereas 55.3±4.5% were CHCl₃-insoluble metabolites. At the same time urine contained 15.5±1.3% CHCl₃-insoluble compounds. Anaerobic incubation of bile with a stool suspension (SS) decreased the polar fraction by 64.8±4.5% (n=6); incubation with a previously autoclaved SS decreased it only by 12.7±2.7%. Preincubation of SS with carbenicillin, cephalotin and ampicillin to depress bacterial growth largely suppressed the metabolic activity. TLC-analysis revealed that the decrease in the polar fraction corresponded to an increase of M, whilst MD, digoxin and B were almost unaltered. The results imply that B and M were formed in the liver, B was preferentially eliminated unchanged in bile and M was conjugated to CHCl₃-insoluble compounds prior to excretion. The polar conjugates were split by bacterial enzymes in the colon to yield M, which could be detected in faeces.