TY - JOUR
T1 - In vivo glucuronidation activity of drugs in neonates
T2 - Extensive interindividual variability despite their young age
AU - Allegaert, Karel
AU - Vanhaesebrouck, Sophie
AU - Verbesselt, Rene
AU - Van Den Anker, John N.
N1 - © 2009 Lippincott Williams & Wilkins, Inc.
PY - 2009/8
Y1 - 2009/8
N2 - Compared with phase I isoenzymes, data on isoenzyme-specific phenotypic activity of uridine diphosphate glucuronosyltransferase (UGT) and its covariates in neonates are limited. In vivo observations on morphine, paracetamol (acetaminophen), and propofol disposition throughout childhood confirm the overall low-glucuronidation activity in neonates observed in in vitro studies. In addition to the phenotypic low-glucuronidation activity, in vivo observations of bilirubin (UGT1A1), morphine (UGT2B7), paracetamol (UGT1A6), and propofol (UGT1A9) glucuronidation in neonates display extensive interindividual variability, only in part explained by postmenstrual and postnatal age. Covariates like disease state characteristics (decreased morphine metabolism during therapeutic head cooling), genetic polymorphisms (UGT1A1 genetic variants and differences in bilirubin metabolism), or environmental factors (increased urinary excretion of paracetamol-glucuronide by repeated administration of paracetamol) further contribute to this variability. A focused approach to unveil covariates of the interindividual range is needed to improve our knowledge on drug disposition in early life.
AB - Compared with phase I isoenzymes, data on isoenzyme-specific phenotypic activity of uridine diphosphate glucuronosyltransferase (UGT) and its covariates in neonates are limited. In vivo observations on morphine, paracetamol (acetaminophen), and propofol disposition throughout childhood confirm the overall low-glucuronidation activity in neonates observed in in vitro studies. In addition to the phenotypic low-glucuronidation activity, in vivo observations of bilirubin (UGT1A1), morphine (UGT2B7), paracetamol (UGT1A6), and propofol (UGT1A9) glucuronidation in neonates display extensive interindividual variability, only in part explained by postmenstrual and postnatal age. Covariates like disease state characteristics (decreased morphine metabolism during therapeutic head cooling), genetic polymorphisms (UGT1A1 genetic variants and differences in bilirubin metabolism), or environmental factors (increased urinary excretion of paracetamol-glucuronide by repeated administration of paracetamol) further contribute to this variability. A focused approach to unveil covariates of the interindividual range is needed to improve our knowledge on drug disposition in early life.
UR - http://www.scopus.com/inward/record.url?scp=68449093196&partnerID=8YFLogxK
U2 - 10.1097/FTD.0b013e3181a8cc0a
DO - 10.1097/FTD.0b013e3181a8cc0a
M3 - Review article
C2 - 19494793
AN - SCOPUS:68449093196
SN - 0163-4356
VL - 31
SP - 411
EP - 415
JO - Therapeutic Drug Monitoring
JF - Therapeutic Drug Monitoring
IS - 4
ER -