Quantitative studies on acid hydrolysis of digitoxin

Area of Science:

• Pharmacology
• Gastroenterology
• Drug Metabolism

Background:

• Digitoxin is a cardiac glycoside used to treat heart conditions.
• Understanding digitoxin's stability in the gastrointestinal tract is crucial for optimizing its therapeutic efficacy.

Purpose of the Study:

• To investigate the hydrolysis of digitoxin in simulated gastric conditions (hydrochloric acid and human gastric juice).
• To assess the impact of gastric hydrolysis on digitoxin bioavailability.
• To examine the absorption kinetics and bioavailability of liquid digitoxin in patients.

Main Methods:

• Incubation of 3H(G)-digitoxin with hydrochloric acid and human gastric juice at varying temperatures and pH.
• Extraction using dichloromethane and separation of radioactive metabolites via thin-layer chromatography (TLC).
• Quantification using a radiochromatogram scanner and radioimmunological measurements of blood levels in patients.

Main Results:

• Digitoxin underwent significant hydrolysis within 10-60 minutes in acidic conditions (pH 1-2) and gastric juice.
• Degradation products included digitoxigeninbis-digitoxoside, digitoxigenin-mono-digitoxoside, and digitoxigenin.
• Patient studies showed significant inter-individual differences in digitoxin absorption kinetics and bioavailability.

Conclusions:

• Digitoxin is unstable in the acidic environment of the stomach, leading to substantial hydrolysis.
• The extent of hydrolysis suggests a significant reduction in digitoxin bioavailability.
• Variability in patient absorption kinetics highlights the need for personalized dosing strategies.