title: Do CYP2D6 genotypes reflect oxycodone requirements for cancer patients treated for cancer pain? A cross-sectional multicentre study.
abstract: OBJECTIVE
  Opioids are recommended by the World Health Organization for moderate to severe cancer pain. Oxycodone is one of the most commonly used opioids and is metabolized in the liver by CYP3A4 and CYP2D6 enzymes. The aim of this cross-sectional study was to assess the relationship between oxycodone pharmacokinetics, pharmacodynamics and the CYP2D6 genotypes "poor metaboliser" (PM), "extensive metaboliser" (EM) and "ultra-rapid metaboliser" (URM) in a cohort of patients with cancer pain.
  
  
  METHODS
  The patients were genotyped for the most common CYP2D6 variants and serum concentrations of oxycodone and metabolites were determined. Pain was assessed using the Brief Pain Inventory (BPI). The EORTC QLQ-C30 was used to assess the symptoms of tiredness and nausea. Cognitive function was assessed by the Mini Mental State (MMS) examination. Associations were examined by analyses of variance (ANOVA) and covariance (ANCOVA), or ordinal logistic regressions with and without covariates.
  
  
  RESULTS
  The sample consisted of 27 PM, 413 EM (including heterozygotes) and 10 URM. PM had lower oxymorphone and noroxymorphone serum concentrations and oxymorphone to oxycodone ratios than EM and URM. No differences between PM, EM and URM in pain intensity, nausea, tiredness or cognitive function was found.
  
  
  CONCLUSIONS
  CYP2D6 genotypes caused expected differences in pharmacokinetics, but they had no pharmacodynamic consequence. CYP2D6 genotypes did not influence pain control, the adverse symptoms nausea and sedation or the risk for cognitive failure in this study of patients treated with oxycodone for cancer pain.
authors: Pain and Palliation Research Group, Faculty of Medicine, Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, 7489, Trondheim, Norway. trine.n.andreassen@ntnu.no
authors: Trine Naalsund
authors: TN
authors: Andreassen
authors: Ingrid
authors: I
authors: Eftedal
authors: Pål
authors: P
authors: Klepstad
authors: Andrew
authors: A
authors: Davies
authors: Kristin
authors: K
authors: Bjordal
authors: Staffan
authors: S
authors: Lundström
authors: Stein
authors: S
authors: Kaasa
authors: Ola
authors: O
authors: Dale
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D001711:Biotransformation; D059350:Chronic Pain / Q000188:drug therapy* / Q000209:etiology; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D016903:Drug Monitoring; D005060:Europe; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009019:Morphinans / Q000097:blood; D009369:Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D010098:Oxycodone / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D010111:Oxymorphone / Q000097:blood; D011110:Polymorphism, Genetic; D012720:Severity of Illness Index
chemical_list: D000701:Analgesics, Opioid; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D009019:Morphinans; C526569:noroxymorphone; D010111:Oxymorphone; D010098:Oxycodone; D019389:Cytochrome P-450 CYP2D6