Digoxin pharmacokinetics in congestive heart failure

Area of Science:

• Pharmacology
• Cardiology
• Clinical Pharmacy

Background:

• Congestive heart failure (CHF) can alter drug pharmacokinetics.
• Digoxin is a common medication for heart failure, but its optimal dosing in CHF is debated.
• Previous assumptions suggested reduced digoxin absorption or increased distribution in heart failure.

Purpose of the Study:

• To compare the steady-state pharmacokinetics of oral digoxin in patients with and without marked right-sided congestive heart failure.
• To evaluate the impact of heart failure compensation on digoxin serum concentrations and pharmacokinetic parameters.
• To determine the appropriateness of supplemental digoxin dosing based on serum levels in heart failure patients.

Main Methods:

• Eight hospitalized patients with right-sided congestive heart failure were studied.
• Digoxin pharmacokinetics were assessed during acute heart failure and after compensation.
• Serum digoxin concentrations, half-life, absorption, and volume of distribution were analyzed.

Main Results:

• Significant intersubject variability in serum digoxin concentrations was observed.
• Digoxin concentrations over 24 hours were similar or higher during heart failure compared to compensated states.
• No significant difference in digoxin elimination half-life was found between the two states.
• The ratio of absorbed digoxin dose to apparent volume of distribution increased by 37% in heart failure (P < 0.05).

Conclusions:

• The prevailing notion that supplemental digoxin doses are needed due to reduced serum concentrations in heart failure is unwarranted.
• Increased absorption fraction relative to volume of distribution in heart failure may explain similar or higher serum concentrations.
• Dosing adjustments for digoxin in heart failure should consider factors beyond simple serum concentration monitoring.