title: Morphine clearance in children: does race or genetics matter?
abstract: OBJECTIVE
  Interindividual variability in analgesic response and adverse effects of opioids because of narrow therapeutic indices are major clinical problems. Morphine is an opioid commonly used in children to manage perioperative pain. Al-though size and age often are considered primary covariates for morphine pharmacokinetic models, the impact of other factors important in personalizing care such as race and genetic variations on morphine disposition is not well documented.
  
  
  METHODS
  Genotype blinded clinical observational pharmacokinetic study. One hundred forty-six African American and Caucasian children scheduled for elective outpatient adenotonsillectomy were enrolled in our prospective genotype blinded observational study with standard perioperative clinical care.
  
  
  METHODS
  Tertiary care pediatric institution.
  
  
  METHODS
  Morphine bolus for intraoperative analgesia in children and pharmacokinetic analyses in different races.
  
  
  METHODS
  Pharmacokinetics and pharmacogenetics of intravenous morphine in a homogeneous pediatric outpatient surgical pain population were evaluated.
  
  
  RESULTS
  The authors observed that African American children have higher morphine clearance than Caucasian children. The increased clearance is directed toward the formation of morphine-3-glucuronide formation, rather than the formation of morphine-6-glucuronide. Common uridine diphosphate glucuronosyl transferase (UGT) 2B7 genetic variations (2161C>T and 802C>T) were not associated with observed racial differences in morphine's clearance although the wild type of the UGT2B7 isozyme is more prevalent in the African Americans.
  
  
  CONCLUSIONS
  Race of the child is an important factor in perioperative intravenous morphine's clearance and its potential role in personalizing analgesia with morphine needs further investigation.
authors.affiliation: Department of Anesthesia, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors.forename: Senthilkumar
authors.initials: S
authors.lastname: Sadhasivam
authors.forename: Elke H J
authors.initials: EH
authors.lastname: Krekels
authors.forename: Vidya
authors.initials: V
authors.lastname: Chidambaran
authors.forename: Hope R
authors.initials: HR
authors.lastname: Esslinger
authors.forename: Pornswan
authors.initials: P
authors.lastname: Ngamprasertwong
authors.forename: Kejian
authors.initials: K
authors.lastname: Zhang
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Fukuda
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Vinks
mesh_terms: D000293:Adolescent; D001741:Black or African American / Q000235:genetics; D000701:Analgesics, Opioid / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002648:Child; D005260:Female; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007206:Individuality; D008297:Male; D009020:Morphine / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D009022:Morphine Derivatives / Q000378:metabolism; D010147:Pain Measurement / Q000379:methods; D010149:Postoperative Pain / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D010597:Pharmacogenetics / Q000379:methods; D011446:Prospective Studies; D044465:White People / Q000235:genetics
chemical_list: D000701:Analgesics, Opioid; D009022:Morphine Derivatives; C035349:morphine-6-glucuronide; D009020:Morphine; C491474:UGT2B7 protein, human; D014453:Glucuronosyltransferase; C018108:morphine-3-glucuronide