Pharmacokinetics and safety of prolonged paracetamol treatment in neonates: An interventional cohort study

Area of Science:

• Neonatal pharmacology
• Pediatric pain management
• Drug metabolism and safety

Background:

• Neonatal pain is a significant concern requiring effective management.
• Paracetamol (acetaminophen) is commonly used for pain relief in neonates.
• Data on the safety and pharmacokinetics of prolonged paracetamol use (>72 hours) in this population are limited.

Purpose of the Study:

• To investigate the pharmacokinetics of paracetamol in neonates receiving prolonged treatment for pain.
• To assess the safety profile of extended paracetamol administration in neonates, focusing on liver function.
• To evaluate potential changes in paracetamol metabolism with prolonged use.

Main Methods:

• A pharmacokinetic study involving 48 neonates receiving oral or intravenous paracetamol for pain.
• Collection of 126 plasma samples for measurement of paracetamol and its metabolites.
• Assessment of liver safety markers (alanine aminotransferase, bilirubin) at different time points during treatment.

Main Results:

• Thirty-eight neonates received paracetamol for over 72 hours, with a median dose of 10.1 mg/kg.
• No significant differences in liver safety markers were observed between short-term (<72h) and prolonged (>72h) paracetamol use.
• Pharmacokinetic parameters including volume of distribution, clearance, steady-state concentration, and half-life were estimated for neonates.

Conclusions:

• Prolonged paracetamol administration in neonates does not appear to induce liver injury.
• No significant alterations in paracetamol metabolism were detected with extended use.
• The findings support the safety of carefully monitored, prolonged paracetamol use for neonatal pain management.