title: CYP2D6 polymorphisms and codeine analgesia in postpartum pain management: a pilot study.
abstract: BACKGROUND
  Codeine, a common opiate prescribed for pain postcesarean section (c-section), is biotransformed by the highly polymorphic Cytochrome P450 enzyme 2D6 (CYP2D6). Ultrarapid metabolizers (UMs), individuals with multiple active copies of CYP2D6, can biotranform up to 50% more codeine into morphine than normal individuals can. In contrast, poor metabolizers (PMs), individuals who have no active CYP2D6 genes, convert almost no codeine into morphine and as a result may take multiple doses of codeine without attaining analgesia.
  
  
  OBJECTIVE
  The aim was to study the relationship between CYP2D6 genotype and codeine analgesia among women recovering from c-section.
  
  
  METHODS
  Forty-five mothers prescribed codeine provided a blood sample for CYP2D6 genotyping and recorded their pain level 4 times a day for 3 days immediately after a c-section. Codeine was used on an as-needed basis; doses and times were recorded. The relationship between CYP2D6 genotype, pain scores, need for codeine, and adverse events was studied. Theoretical morphine dose, based on CYP2D6 genotype, was estimated.
  
  
  RESULTS
  Women at the genotypic extremes reported codeine effects consistent with their genotype: the 2 PMs of codeine reported no analgesia as a result of taking codeine, whereas 2 of the 3 UMs reported immediate pain relief from codeine but stopped taking it due to dizziness and constipation. Much larger numbers are needed to study similar correlations among extensive and intermediate metabolizers.
  
  
  CONCLUSIONS
  In this pilot study, the extreme CYP2D6 genotypes (PMs and UMs) seemed to predict pain response and adverse events. Larger sample sizes are needed to correlate the range of genotypes with pain response.
authors: Department of Pharmaceutical Sciences, University of Toronto, Ontario, Canada.
authors: Sondra
authors: S
authors: VanderVaart
authors: Howard
authors: H
authors: Berger
authors: Johanna
authors: J
authors: Sistonen
authors: Parvaz
authors: P
authors: Madadi
authors: Ilan
authors: I
authors: Matok
authors: Violette M G J
authors: VM
authors: Gijsen
authors: Saskia N
authors: SN
authors: de Wildt
authors: Anna
authors: A
authors: Taddio
authors: Colin J D
authors: CJ
authors: Ross
authors: Bruce C
authors: BC
authors: Carleton
authors: Michael R
authors: MR
authors: Hayden
authors: Gideon
authors: G
authors: Koren
mesh_terms: D000328:Adult; D000698:Analgesia; D000701:Analgesics, Opioid / Q000493:pharmacokinetics / Q000627:therapeutic use; D001711:Biotransformation; D016022:Case-Control Studies; D002585:Cesarean Section / Q000379:methods; D003061:Codeine / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D015331:Cohort Studies; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D009020:Morphine / Q000097:blood; D010147:Pain Measurement / Q000379:methods; D010149:Postoperative Pain / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D010865:Pilot Projects; D011110:Polymorphism, Genetic / Q000235:genetics*; D049590:Postpartum Period; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D009020:Morphine; D019389:Cytochrome P-450 CYP2D6; D003061:Codeine