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Morphine metabolism in children.

I A Choonara1, P McKay, R Hain

  • 1Division of Clinical Pharmacology, University Hospital, Uppsala, Sweden.

British Journal of Clinical Pharmacology
|November 1, 1989
PubMed
Summary
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Morphine metabolism differs significantly between neonates and children, with higher clearance and enhanced glucuronidation in older children. This suggests improved morphine processing after the neonatal period.

Area of Science:

  • Pharmacology
  • Pediatric Medicine
  • Drug Metabolism

Background:

  • Morphine is a widely used analgesic in pediatric populations.
  • Understanding morphine metabolism is crucial for optimizing pain management and minimizing adverse effects in neonates and children.
  • Developmental changes in drug metabolism can significantly impact pharmacokinetic profiles.

Purpose of the Study:

  • To investigate and compare the metabolism of morphine in premature neonates and children.
  • To assess the impact of age on morphine clearance and glucuronidation pathways.
  • To determine the developmental trajectory of morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) formation.

Main Methods:

  • Continuous infusion of morphine was administered to 12 children and nine premature neonates.

Related Experiment Videos

  • Plasma concentrations of morphine, M3G, and M6G were measured.
  • Plasma clearance and metabolite-to-parent drug ratios were calculated and compared between the two groups.

    • Main Results:

    • Mean plasma clearance of morphine was significantly higher in children (25.7 ml/min/kg) compared to neonates (4.7 ml/min/kg).
    • Detectable concentrations of M3G and M6G were found in plasma and/or urine of both groups.
    • M3G/morphine and M6G/morphine ratios were significantly higher in children, indicating enhanced glucuronidation capacity.
    • No significant difference was observed in the M3G/M6G ratio, suggesting parallel development of these pathways.

    Conclusions:

    • Morphine clearance and glucuronidation are significantly enhanced after the neonatal period.
    • These findings highlight important developmental changes in morphine metabolism that influence its efficacy and safety in pediatric patients.
    • The parallel development of M3G and M6G pathways suggests coordinated maturation of the underlying enzymatic systems.