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The maturation of morphine clearance and metabolism
T I McRorie1, A M Lynn, M K Nespeca
1Department of Pharmacy, School of Pharmacy, University of Washington, Seattle 98195.
Insights
Morphine clearance in children reaches adult levels by 6 months to 2.5 years of age. Morphine sulfate clearance does not appear to be enhanced in early infancy compared to glucuronidation.
Area of Science:
- Pharmacology
- Pediatric Medicine
- Drug Metabolism
Background:
- Morphine is a widely used analgesic in pediatric patients.
- Understanding morphine clearance in children is crucial for safe and effective dosing.
- Previous studies suggested differences in drug metabolism maturation between neonates and adults.
Purpose of the Study:
- To determine the age at which morphine clearance in children approximates adult values.
- To investigate the maturation of morphine metabolism pathways, specifically glucuronidation and sulfation, in pediatric populations.
Main Methods:
- A patient series study was conducted involving 49 children (1 day to 2.5 years) receiving continuous intravenous morphine infusion.
- Blood and urine samples were collected to measure morphine concentrations and calculate clearance, half-life, and metabolite formation.
- Renal and hepatic functions were assessed to ensure normal metabolic capacity.
Main Results:
- Morphine clearance significantly increased with age, ranging from 5 mL/kg/min in neonates to 21 mL/kg/min in infants over 6 months.
- Age-correlated increases were observed in morphine glucuronide formation clearance.
- Morphine sulfate formation clearance and renal clearance of morphine were independent of age.
Conclusions:
- Pediatric morphine clearance reaches adult levels between 6 months and 2.5 years of age.
- Contrary to some prior research, morphine sulfate clearance does not seem to be disproportionately enhanced over glucuronidation in early infancy.
- These findings have implications for optimizing morphine dosing strategies in children.
Objective:
To determine how early in childhood the clearance of morphine sulfate reaches that in adults.
Design:
Patient series.
Setting:
Children's Hospital and Medical Center, Seattle, Wash.
Participants:
Forty-nine children aged 1 day to 2.5 years with normal renal and hepatic function. All children were receiving a constant rate intravenous infusion of morphine for postoperative analgesia for greater than 24 hours.
Interventions:
Blood and urine samples were collected during infusion and immediately after discontinuation of the morphine infusion.
Measurements:
Morphine concentrations were determined and clearance was calculated using the infusion data. Half-life and volume of distribution were calculated using the postinfusion data. The formation of metabolites was evaluated using the urine data. Morphine clearance increased with age, median clearances ranging from 5 mL/kg per minute in neonates aged 1 to 7 days to 21 mL/kg per minute in infants aged 6 months and older. This change in clearance correlated with age. The formation clearance of morphine glucuronide was correlated with age, whereas the formation clearance of morphine sulfate and the renal clearance of morphine were independent of age.
Conclusions:
Morphine clearance reaches adult values by age 6 months to 2.5 years. In contrast to previous reports on the maturation of sulfate conjugation, it does not appear that morphine sulfate clearance is enhanced relative to glucuronidation in early infancy.