title: CYP2D6 pharmacogenetic and oxycodone pharmacokinetic association study in pediatric surgical patients.
abstract: OBJECTIVE
  Oxycodone is partly metabolized to the active metabolite oxymorphone by hepatic CYP2D6 in the liver. Significant genetic variability in CYP2D6 activity affects oxymorphone formation. This study aimed to associate CYP2D6 genotype and oxycodone's metabolism.
  
  
  METHODS
  30 children were administered oral oxycodone postoperatively. Plasma levels of oxycodone and oxymorphone, and CYP2D6 genotype were analyzed. CYP2D6 genotype and oxycodone metabolism phenotype were determined based on CYP2D6 total activity score (TAS) and metabolism phenotype: poor metabolizer (PM), intermediate metabolizer (IM), extensive metabolizer (EM) or ultrarapid metabolizer (UM).
  
  
  RESULTS
  Compared with PM/IM subjects, significantly greater oxymorphone exposure was seen in EM subjects (p = 0.02 for Cmax, p = 0.016 for AUC0-6and p = 0.026 for AUC0-24). Similarly, higher TAS value was found to be associated with greater oxymorphone exposure. Higher conversion of oxycodone to oxymorphone was observed in EM subjects compared with PM/IM subjects (p = 0.0007 for Cmax, p = 0.001 for AUC0-6and p = 0.004 for AUC0-24).
  
  
  CONCLUSIONS
  CYP2D6 phenotypes explain metabolism of oxycodone in children, and oxymorphone exposure is higher in CYP2D6 EM phenotype. Further studies are needed to predict the occurrence of adverse event and tailor oxycodone dose for a specific CYP2D6 phenotype.
authors.affiliation: Department of Anesthesia, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 2001, Cincinnati, OH 45229, USA.|Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Balyan
authors.affiliation: Department of Anesthesia, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 2001, Cincinnati, OH 45229, USA.|Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Mecoli
authors.affiliation: Department of Anesthesia, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 2001, Cincinnati, OH 45229, USA.|Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Raja
authors.initials: R
authors.lastname: Venkatasubramanian
authors.affiliation: Department of Anesthesia, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 2001, Cincinnati, OH 45229, USA.|Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA.
authors.forename: Vidya
authors.initials: V
authors.lastname: Chidambaran
authors.affiliation: Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA.
authors.forename: Nichole
authors.initials: N
authors.lastname: Kamos
authors.affiliation: Department of Anesthesia, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 2001, Cincinnati, OH 45229, USA.|Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA.
authors.forename: Smokey
authors.initials: S
authors.lastname: Clay
authors.affiliation: Department of Anesthesia, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 2001, Cincinnati, OH 45229, USA.|Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Moore
authors.affiliation: Department of Anesthesia, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 2001, Cincinnati, OH 45229, USA.|Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA.
authors.forename: Jagroop
authors.initials: J
authors.lastname: Mavi
authors.affiliation: Department of Anesthesia, Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Chris D
authors.initials: CD
authors.lastname: Glover
authors.affiliation: Department of Anesthesiology & Pain Management, University of Texas Southwestern & Children's Medical Center, Dallas, TX 75390, USA.|Outcome Research Consortium, Cleveland, OH 44195, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Szmuk
authors.affiliation: Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.|Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Vinks
authors.affiliation: Department of Anesthesia, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 2001, Cincinnati, OH 45229, USA.|Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA.
authors.forename: Senthilkumar
authors.initials: S
authors.lastname: Sadhasivam
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D010098:Oxycodone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010149:Postoperative Pain / Q000097:blood* / Q000235:genetics* / Q000517:prevention & control; D010597:Pharmacogenetics / Q000379:methods*; D010865:Pilot Projects; D011446:Prospective Studies
chemical_list: D000701:Analgesics, Opioid; D010098:Oxycodone; D019389:Cytochrome P-450 CYP2D6
keywords: CYP2D6; oxycodone; pediatrics; pharmacogenetics; pharmacokinetics; surgical pain