Postmortem digoxin tissue concentration and organ content in infancy and childhood

Area of Science:

• Pharmacology
• Pediatric Medicine
• Forensic Toxicology

Background:

• Digoxin is a cardiac glycoside used to treat heart failure and arrhythmias.
• Understanding digoxin distribution is crucial for therapeutic management and forensic investigations, especially in pediatric populations.
• Infants and children exhibit different pharmacokinetic profiles compared to adults.

Purpose of the Study:

• To determine the tissue distribution of digoxin in infants and children.
• To establish upper therapeutic concentration thresholds for digoxin in various tissues.
• To examine the forensic implications of digoxin overdosage in pediatric cases.

Main Methods:

• Analysis of digoxin concentrations in tissues and organs from 36 pediatric patients.
• Categorization of patients based on treatment duration (short-term vs. long-term) and administration route (intravenous, oral, intramuscular).
• Comparison of digoxin levels between preterm neonates, full-term neonates, and older children.

Main Results:

• Established upper therapeutic concentration thresholds for digoxin in different tissues.
• Demonstrated distinct thresholds for neonates versus older children and adults.
• Observed that chronically digitalized premature infants retain a larger fraction of digoxin in tissues compared to more mature infants and children.
• Noted lower renal digoxin levels in premature infants, correlating with reduced drug excretion.

Conclusions:

• Digoxin tissue and organ concentrations differ significantly between pediatric age groups and adults.
• Established therapeutic concentration thresholds aid in forensic evaluations of digoxin overdosage.
• Premature infants' reduced renal excretion capacity leads to higher digoxin retention, requiring careful dosing considerations.