Quantitative studies on acid hydrolysis of digitoxin.

Hydrolysis of 3H(G)-digitoxin by hydrochloric acid and human gastric juice is described. Incubation temperatures of 37 degrees C and 22 degrees C were chosen for electrolyte solutions, and 37 degrees C for the experiments with gastric juice. After dichloromethane extraction, the radioactive metabolites were separated by thin-layer chromatography, localized and quantified by a radiochromatogram scanner. The degradation products separated by TLC were digitoxigeninbis-digitoxoside, digitoxigenin-mono-digitoxoside, and digitoxigenin. After 10 min of incubation at pH 1, digitoxin amounted to 38.6% of the total radioactivity in electrolyte solution and 37.6% in gastric juice. After 60 min, the percentage of digitoxin decreased to 5.9% and 0%, respectively. After 120 min at 22 degrees C, amounts of unhydrolyzed digitoxin were: at pH 1 55%; and at pH 2 84%. After 10 min at pH 1, and 60 min at pH 2, digitoxin was hydrolyzed to such an extent that bioavailability should have been significantly reduced. Absorption of digitoxin (liquid) from the stomach was studied during gastroscopy in five patients. Among them, significant differences in absorption kinetics and bioavailability existed, as revealed by radioimmunological measurements of the digitoxin blood levels.