CYP2D6 polymorphisms and codeine analgesia in postpartum pain management: A pilot study

Sondra VanderVaart, Howard Berger, Johanna Sistonen, Parvaz Madadi, Ilan Matok, Violette M.G.J. Gijsen, Saskia N. De Wildt, Anna Taddio, Colin J.D. Ross, Bruce C. Carleton, Michael R. Hayden, Gideon Koren

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


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.

Original languageEnglish
Pages (from-to)425-432
Number of pages8
JournalTherapeutic Drug Monitoring
Issue number4
StatePublished - Aug 2011
Externally publishedYes


  • Analgesia
  • CYP2D6
  • Cesarean section
  • Codeine
  • Pharmacodynamics
  • Therapeutic drug monitoring


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