The maturation of morphine clearance and metabolism
T. I. McRorie, A. M. Lynn, M. K. Nespeca, K. E. Opheim and J. T. Slattery
Department of Pharmacy, School of Pharmacy, University of Washington, Seattle 98195.
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.
