Open AccessCould Postnatal Age–Related Uridine Diphosphate Glucuronic Acid Be a Rate‐Limiting Factor in the Metabolism of Morphine During the First Week of Life?
Author(s) -
Liu Tao,
Lewis Tamorah R.,
Moore Jason N.,
Kraft Walter K.,
Gauda Estelle B.,
Sartori David,
Moody David E.,
Gobburu Jogarao V. S.,
Ivaturi Vijay
Publication year - 2019
Publication title -
cpt: pharmacometrics and systems pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 37
ISSN - 2163-8306
DOI - 10.1002/psp4.12407
Subject(s) - glucuronidation , uridine diphosphate , glucuronosyltransferase , uridine , morphine , glucuronic acid , metabolism , population , drug metabolism , pharmacology , bilirubin , enzyme , medicine , chemistry , biochemistry , endocrinology , physiology , polysaccharide , rna , environmental health , gene , microsome
Neonates experience dramatic changes in the disposition of drugs after birth as a result of enzyme maturation and environmental adjustment, challenging therapeutic decision making. In this research, we establish postnatal age, postmenstrual age, and body weight as physiologically reasonable predictors of morphine's clearance in neonates. By integrating knowledge of bilirubin, morphine, and other drugs metabolized by glucuronidation pathways from previously published studies, we hypothesize that uridine diphosphate glucuronic acid, a postnatal age–dependent sugar, plays an important role in the metabolism of morphine during the first week of life. This finding can be extended to other drugs metabolized by uridine diphosphate glucuronosyltransferase pathways in neonates and thus has important clinical implications for the use of drugs in this population.