Hydrolysis of digoxin by acid.

Area of Science:

• Pharmacology
• Gastroenterology

Background:

• Digoxin is a cardiac glycoside with a narrow therapeutic index.
• Understanding digoxin's stability in the gastrointestinal tract is vital for its effective use.

Purpose of the Study:

• To investigate the in vitro and in vivo hydrolysis of digoxin in gastric conditions.
• To determine the extent and products of digoxin degradation under varying acidity.

Main Methods:

• In vitro hydrolysis of [3H]digoxin in HCl and gastric juice at different pH, time, and temperature.
• Separation and quantification of digoxin and its metabolites using thin-layer chromatography and liquid scintillation spectrometry.
• In vivo study in a volunteer receiving [3H]digoxin via nasogastric tube, with gastric fluid and urine analysis.

Main Results:

• Digoxin hydrolysis increased significantly with decreasing pH and increasing incubation time.
• Over 96% hydrolysis occurred at pH 1-2 after 90 minutes in vitro.
• In vivo, digoxigenin was identified in gastric aspirate and all urine specimens, indicating extensive intragastric hydrolysis.

Conclusions:

• Digoxin undergoes predictable and extensive hydrolysis in the stomach, particularly under conditions of high acidity.
• Intragastric hydrolysis of digoxin may significantly impact its absorption and bioavailability.
• Further research is needed to assess the clinical implications of this hydrolysis on digoxin therapy.