title: Putative association of ABCB1 2677G>T/A with oxycodone-induced central nervous system depression in breastfeeding mothers.
abstract: OBJECTIVE
  To assess the effect of maternal CYP2D6, CYP3A5, ABCB1, and OPRM1 polymorphisms in predicting both neonatal and maternal central nervous system depression after oxycodone use during lactation.
  
  
  METHODS
  A nested case-control study in 67 breastfeeding mother-infant pairs exposed to oxycodone was conducted. Cases were defined as parental reports of lethargy in the infant temporally related to oxycodone exposure via breastmilk. Maternal saliva samples were analyzed for 18 polymorphisms in 4 genes, CYP2D6, CYP3A5, OPRM1, ABCB1, involved in oxycodone metabolism and response.
  
  
  RESULTS
  Mothers of symptomatic infants were using oxycodone for a longer period of time during breastfeeding compared with those of asymptomatic infants (P < 0.0001). None of the maternal genetic variants in the 4 genes were associated with oxycodone-induced depression in neonates. However, mothers carrying at least one copy of the ABCB1 2677 T variant had an increased risk of experiencing sedation themselves (odds ratio, 2.35; 95% confidence interval, 1.06-5.28; P = 0.03).
  
  
  CONCLUSIONS
  The ABCB1 2677 T variant may predict oxycodone-induced central nervous system depression in breastfeeding mothers.
authors.affiliation: Department of Pharmacology and Toxicology, University of Toronto, Toronto, Canada.
authors.forename: Jessica
authors.initials: J
authors.lastname: Lam
authors.forename: Lauren
authors.initials: L
authors.lastname: Kelly
authors.forename: Ilan
authors.initials: I
authors.lastname: Matok
authors.forename: Colin J D
authors.initials: CJ
authors.lastname: Ross
authors.forename: Bruce C
authors.initials: BC
authors.lastname: Carleton
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hayden
authors.forename: Parvaz
authors.initials: P
authors.lastname: Madadi
authors.forename: Gideon
authors.initials: G
authors.lastname: Koren
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D001942:Breast Feeding; D016022:Case-Control Studies; D002490:Central Nervous System / Q000187:drug effects*; D002493:Central Nervous System Diseases / Q000139:chemically induced* / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D007774:Lactation / Q000187:drug effects* / Q000235:genetics*; D008895:Milk, Human / Q000378:metabolism; D009035:Mothers; D010098:Oxycodone / Q000009:adverse effects* / Q000493:pharmacokinetics; D020641:Polymorphism, Single Nucleotide
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D010098:Oxycodone