Fasting and postprandial absorption of digoxin from a microencapsulated formulation

Area of Science:

• Pharmacokinetics
• Drug Delivery Systems
• Clinical Pharmacology

Background:

• Digoxin is a cardiac glycoside widely used for treating heart failure and arrhythmias.
• Optimizing digoxin bioavailability and therapeutic efficacy requires understanding its absorption characteristics.
• Enteric-coated formulations aim to control drug release, but their impact on digoxin absorption needs detailed investigation.

Purpose of the Study:

• To compare the pharmacokinetic profiles of digoxin absorption from an enteric-coated granular formulation (CR) versus a rapidly dissolving tablet (L).
• To evaluate the effect of formulation on peak plasma concentrations, time to peak concentration, and overall bioavailability of digoxin.

Main Methods:

• A comparative pharmacokinetic study involving 10 healthy volunteers.
• Administration of a loading dose of digoxin (0.76 mg) in both fasting and postprandial states.
• Quantification of plasma and urine digoxin concentrations using radioimmunoassay.

Main Results:

• Preparation CR showed significantly lower peak plasma digoxin concentrations (p < 0.001) and delayed Tmax (p < 0.001) compared to Preparation L in fasting state.
• Postprandial steady-state peak concentrations were also significantly lower (p < 0.01) and delayed (p < 0.01) with CR.
• Area under the plasma concentration-time curve (AUC) and urinary excretion were significantly reduced for CR (p < 0.01 and p < 0.005, respectively).

Conclusions:

• The enteric-coated granular formulation (CR) markedly reduces the absorption rate of digoxin.
• This reduction in absorption rate comes at the expense of a variable decrease in the overall amount of digoxin absorbed.
• Formulation choice significantly impacts digoxin pharmacokinetics, necessitating careful consideration for optimal therapeutic outcomes.