Postmortem tissue digoxin concentrations in infants and children

Area of Science:

• Pharmacology
• Pediatric Medicine
• Toxicology

Background:

• Digoxin is a cardiac glycoside used to treat heart failure and arrhythmias.
• Infant pharmacokinetics and tissue distribution of digoxin differ from adults.
• Autopsy data provides valuable insights into drug distribution in various age groups.

Purpose of the Study:

• To determine digoxin concentrations in the tissues of premature infants, full-term infants, and older children.
• To compare digoxin tissue distribution across different pediatric age groups.
• To evaluate the potential implications of observed digoxin concentrations on recommended infant dosages.

Main Methods:

• Radioimmunoassay was used to quantify digoxin concentrations.
• Tissues analyzed included the right and left ventricles and kidneys.
• Samples were obtained from deceased individuals across premature infant, full-term infant, and older child populations.

Main Results:

• Infants (premature and full-term) showed significantly higher digoxin concentrations in ventricular tissues (approx. 190 ng/g) compared to older children (approx. 70 ng/g).
• Renal digoxin concentrations were lower in premature infants, potentially linked to immature kidney function.
• A notable disparity in digoxin distribution was observed between infants and older children.

Conclusions:

• Myocardial digoxin concentrations in infants are substantially higher than in older children.
• Lower renal concentrations in premature infants may reflect reduced excretory capacity.
• The high cardiac digoxin levels in infants suggest that standard dosing regimens might be too high.