title: Effect of UGT2B7 -900G>A (-842G>A; rs7438135) on morphine glucuronidation in preterm newborns: results from a pilot cohort.
abstract: OBJECTIVE
  Assess association between UGT2B7 polymorphism -900G>A (rs7438135, also known as -842G>A) with morphine kinetics in preterm newborns undergoing mechanical ventilation.
  
  
  METHODS
  Thirty-four infants were enrolled in a randomized clinical trial and allocated to rapid sequence intubation with remifentanil (1 µg/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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department Clinical Chemistry, Erasmus MC - University Medical Center Rotterdam, The Netherlands.
authors.forename: Maja
authors.initials: M
authors.lastname: Matic
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Norman
authors.forename: Anders
authors.initials: A
authors.lastname: Rane
authors.forename: Olof
authors.initials: O
authors.lastname: Beck
authors.forename: Maria
authors.initials: M
authors.lastname: Andersson
authors.forename: Laure
authors.initials: L
authors.lastname: Elens
authors.forename: Dick
authors.initials: D
authors.lastname: Tibboel
authors.forename: Vineta
authors.initials: V
authors.lastname: Fellman
authors.forename: Ron H N
authors.initials: RH
authors.lastname: van Schaik
mesh_terms: D005260:Female; D056726:Genetic Association Studies; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D009020:Morphine / Q000008:administration & dosage* / Q000097:blood; D009022:Morphine Derivatives / Q000097:blood; D007752:Obstetric Labor, Premature / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010880:Piperidines / Q000008:administration & dosage* / Q000097:blood; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D016032:Randomized Controlled Trials as Topic; D000077208:Remifentanil
chemical_list: D009022:Morphine Derivatives; D010880:Piperidines; C035349:morphine-6-glucuronide; D009020:Morphine; C491474:UGT2B7 protein, human; D014453:Glucuronosyltransferase; C018108:morphine-3-glucuronide; D000077208:Remifentanil
keywords: UGT2B7; morphine; newborns; pharmacokinetics; polymorphism; ventilation