Digoxin-quinidine interaction. Changes in canine tissue concentration from steady state with quinidine

Area of Science:

• Pharmacology
• Toxicology
• Cardiovascular Research

Background:

• Digoxin is a cardiac glycoside used to treat heart failure and arrhythmias.
• Quinidine is an antiarrhythmic drug that can interact with other medications.
• The interaction between digoxin and quinidine can lead to altered drug concentrations and potential toxicity.

Purpose of the Study:

• To investigate the effects of quinidine on tissue distribution of digoxin in dogs.
• To understand the relationship between digoxin tissue levels and observed toxicity.
• To explore the potential for a neurally mediated mechanism in digoxin-quinidine toxicity.

Main Methods:

• Administration of tritiated digoxin to dogs.
• Simultaneous administration of quinidine.
• Measurement of digoxin concentrations in serum and various tissues, including brain and myocardium.
• Comparison of tissue concentrations between control and digoxin-quinidine treated groups.

Main Results:

• Quinidine significantly altered digoxin tissue distribution in dogs.
• Serum digoxin levels increased, while tissue concentrations decreased, except in the brain.
• Brain digoxin concentrations increased by 51% compared to controls.
• Myocardial digoxin levels decreased, correlating with observed toxicity.

Conclusions:

• The digoxin-quinidine interaction in dogs leads to increased brain concentrations and decreased myocardial concentrations of digoxin.
• This altered distribution suggests a neurally mediated toxicity mechanism.
• Further research is needed to assess the impact on digoxin's inotropic effect due to reduced myocardial concentration.