The maturation of morphine clearance and metabolism.
OBJECTIVE
To determine how early in childhood the clearance of morphine sulfate reaches that in adults.


METHODS
Patient series.


METHODS
Children's Hospital and Medical Center, Seattle, Wash.


METHODS
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.


METHODS
Blood and urine samples were collected during infusion and immediately after discontinuation of the morphine infusion.


METHODS
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.
McRorie
T I
TI
Department of Pharmacy, School of Pharmacy, University of Washington, Seattle 98195.
Lynn
A M
AM
Nespeca
M K
MK
Opheim
K E
KE
Slattery
J T
JT
D000698:Analgesia; D002675:Child, Preschool; D005965:Glucuronates / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007668:Kidney / Q000378:metabolism; D008657:Metabolic Clearance Rate; D009020:Morphine / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D011182:Postoperative Care; D013431:Sulfates / Q000378:metabolism; D013997:Time Factors
D005965:Glucuronates; D013431:Sulfates; D009020:Morphine