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

Maja Matic, Elisabeth Norman, Anders Rane, Olof Beck, Maria Andersson, Laure Elens, Dick Tibboel, Vineta Fellman, Ron H. N. van Schaik

Research output: Contribution to journalArticlepeer-review

20 Citations (SciVal)

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.
Original languageEnglish
Pages (from-to)1589-1597
JournalPharmacogenomics
Volume15
Issue number12
DOIs
Publication statusPublished - 2014

Subject classification (UKÄ)

  • Pediatrics

Keywords

  • morphine
  • newborns
  • pharmacokinetics
  • polymorphism
  • UGT2B7
  • ventilation

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