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Effect of UGT2B7-900G > A (-842G > A; rs7438135) on morphine glucuronidation in preterm newborns: results from a pilot cohort

Matic, Maja; Norman, Elisabeth LU ; Rane, Anders; Beck, Olof; Andersson, Maria; Elens, Laure; Tibboel, Dick; Fellman, Vineta LU and van Schaik, Ron H. N. (2014) In Pharmacogenomics 15(12). p.1589-1597
Abstract
Aim: Assess association between UGT2B7 polymorphism -900G>A (rs7438135, also known as -842G>A) with morphine kinetics in preterm newborns undergoing mechanical ventilation. Materials & methods: Thirty-four infants were enrolled in a randomized clinical trial and allocated to rapid sequence intubation with remifentanil (1 mu g/kg) or morphine (0.3 mg/kg). The latter group was included in our study. Results: Morphine plasma concentrations at 20 min post intubation were associated with postnatal age (p = 0.017) and UGT2B7 -900G>A (p = 0.036). UGT2B7 -900A allele carriers (n = 13) had lower morphine levels compared with UGT2B7 -900G/G patients (n = 2). Morphine-3-glucuronide and morphine-6-glucuronide plasma concentrations were... (More)
Aim: Assess association between UGT2B7 polymorphism -900G>A (rs7438135, also known as -842G>A) with morphine kinetics in preterm newborns undergoing mechanical ventilation. Materials & methods: Thirty-four infants were enrolled in a randomized clinical trial and allocated to rapid sequence intubation with remifentanil (1 mu g/kg) or morphine (0.3 mg/kg). The latter group was included in our study. Results: Morphine plasma concentrations at 20 min post intubation were associated with postnatal age (p = 0.017) and UGT2B7 -900G>A (p = 0.036). UGT2B7 -900A allele carriers (n = 13) had lower morphine levels compared with UGT2B7 -900G/G patients (n = 2). Morphine-3-glucuronide and morphine-6-glucuronide plasma concentrations were only found to be associated with gestational and postnatal age. However, -900A allele carriers had a higher morphine-3-glucuronide: morphine metabolic ratio compared with patients genotyped as -900G/G (p = 0.005), as determined by linear regression. Conclusion: Our small pilot study illustrates that in addition to gestational and postnatal age, the UGT2B7 -900G>A polymorphism significantly alters morphine pharmacokinetics in preterm infants. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
morphine, newborns, pharmacokinetics, polymorphism, UGT2B7, ventilation
in
Pharmacogenomics
volume
15
issue
12
pages
1589 - 1597
publisher
Future Medicine Ltd.
external identifiers
  • wos:000344180300005
  • scopus:84908139332
ISSN
1462-2416
DOI
10.2217/PGS.14.115
language
English
LU publication?
yes
id
1ef01f8d-7b39-490e-a04e-9df396af97f1 (old id 4875960)
date added to LUP
2015-01-07 10:29:24
date last changed
2017-07-09 03:15:44
@article{1ef01f8d-7b39-490e-a04e-9df396af97f1,
  abstract     = {Aim: Assess association between UGT2B7 polymorphism -900G>A (rs7438135, also known as -842G>A) with morphine kinetics in preterm newborns undergoing mechanical ventilation. Materials & methods: Thirty-four infants were enrolled in a randomized clinical trial and allocated to rapid sequence intubation with remifentanil (1 mu g/kg) or morphine (0.3 mg/kg). The latter group was included in our study. Results: Morphine plasma concentrations at 20 min post intubation were associated with postnatal age (p = 0.017) and UGT2B7 -900G>A (p = 0.036). UGT2B7 -900A allele carriers (n = 13) had lower morphine levels compared with UGT2B7 -900G/G patients (n = 2). Morphine-3-glucuronide and morphine-6-glucuronide plasma concentrations were only found to be associated with gestational and postnatal age. However, -900A allele carriers had a higher morphine-3-glucuronide: morphine metabolic ratio compared with patients genotyped as -900G/G (p = 0.005), as determined by linear regression. Conclusion: Our small pilot study illustrates that in addition to gestational and postnatal age, the UGT2B7 -900G>A polymorphism significantly alters morphine pharmacokinetics in preterm infants.},
  author       = {Matic, Maja and Norman, Elisabeth and Rane, Anders and Beck, Olof and Andersson, Maria and Elens, Laure and Tibboel, Dick and Fellman, Vineta and van Schaik, Ron H. N.},
  issn         = {1462-2416},
  keyword      = {morphine,newborns,pharmacokinetics,polymorphism,UGT2B7,ventilation},
  language     = {eng},
  number       = {12},
  pages        = {1589--1597},
  publisher    = {Future Medicine Ltd.},
  series       = {Pharmacogenomics},
  title        = {Effect of UGT2B7-900G > A (-842G > A; rs7438135) on morphine glucuronidation in preterm newborns: results from a pilot cohort},
  url          = {http://dx.doi.org/10.2217/PGS.14.115},
  volume       = {15},
  year         = {2014},
}