Single- and multiple-dose kinetics of intravenous digoxin

Area of Science:

• Pharmacology
• Clinical Pharmacokinetics

Background:

• Digoxin is a cardiac glycoside used to treat heart failure and arrhythmias.
• Understanding digoxin's pharmacokinetic behavior is crucial for optimizing therapeutic efficacy and minimizing toxicity.

Purpose of the Study:

• To compare digoxin's pharmacokinetic profiles after single and multiple intravenous doses.
• To assess the predictability of single-dose kinetics for multiple-dose outcomes.

Main Methods:

• Nine healthy male subjects received single intravenous doses (0.5, 1.0, 1.5 mg) and a 10-day multiple-dose regimen (0.25 mg/day).
• Serum digoxin concentrations were measured over 36 hours (single dose) and 72 hours post-last dose (multiple dose).
• Key pharmacokinetic parameters including half-life, volume of distribution, and clearance were calculated and compared.

Main Results:

• Multiple-dose therapy showed a longer elimination half-life (38.0 hr) compared to single-dose (27.9 hr).
• Volume of distribution increased significantly with multiple dosing (7.4 L/kg vs 5.5 L/kg).
• Total clearance remained consistent, but single-dose kinetics poorly predicted drug accumulation and washout.

Conclusions:

• Digoxin clearance is not systematically altered by multiple-dose therapy.
• Single-dose pharmacokinetic parameters are inadequate predictors of digoxin accumulation and elimination during chronic dosing.
• Therapeutic drug monitoring is essential for managing digoxin therapy effectively.