Document Detail

Morphine metabolism in acutely ill preterm newborn infants.
MedLine Citation:
PMID:  1578319     Owner:  NLM     Status:  MEDLINE    
To examine the manner in which morphine is metabolized in acutely ill premature infants, we measured the levels of morphine, morphine-3- and -6-glucuronides, and codeine in timed urine specimens and paired plasma specimens at 4 hours and 24 hours after a single dose of morphine in 16 preterm infants (less than 32 weeks of gestational age). A large amount of unmetabolized morphine was found in the urine in 13 (81.2%) of the 16 infants at 4 hours; in 12 of them, morphine was excreted even at 24 hours. Urinary morphine levels varied greatly; the coefficient of variation was 130% at 4 hours and 118% at 24 hours. Codeine was not found in any of the infants. In 10 (62.5%) of the 16 infants, at least one metabolite was found in either plasma or urine. Plasma and urinary levels of morphine conjugates also varied greatly among these 10 infants (coefficient of variation: 109% to 317%). All six infants (37.5%) who had no metabolites excreted large amounts of unmetabolized morphine in the urine for up to 24 hours. Birth weight, gestational age, postnatal age, systemic blood pressure, and other clinical or physiologic variables did not differ significantly between the 10 infants who had morphine conjugates and the six who did not. We conclude that (1) nearly two thirds of acutely ill preterm infants born at less than 32 weeks of gestational age conjugate morphine; (2) irrespective of their ability to produce morphine conjugates, preterm infants excrete large amounts of morphine unmetabolized, as late as 24 hours after a single dose; (3) morphine handling patterns are highly variable among premature infants, and no obvious factors account for the variability; and (4) such variability in morphine handling in general, and the production of the highly potent morphine-6-glucuronide in particular, could explain the variance in morphine pharmacokinetic measures and in the clinical responses to morphine during the newborn period.
R Bhat; M Abu-Harb; G Chari; A Gulati
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of pediatrics     Volume:  120     ISSN:  0022-3476     ISO Abbreviation:  J. Pediatr.     Publication Date:  1992 May 
Date Detail:
Created Date:  1992-06-05     Completed Date:  1992-06-05     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0375410     Medline TA:  J Pediatr     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  795-9     Citation Subset:  AIM; IM    
Department of Pediatrics, University of Illinois, Chicago.
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MeSH Terms
Chromatography, High Pressure Liquid
Codeine / analysis
Infant, Newborn
Infant, Premature, Diseases / drug therapy,  metabolism*
Morphine / metabolism*,  therapeutic use
Morphine Derivatives / analysis
Respiration, Artificial
Reg. No./Substance:
0/Morphine Derivatives; 20290-09-9/morphine-3-glucuronide; 20290-10-2/morphine-6-glucuronide; 57-27-2/Morphine; 76-57-3/Codeine

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