title: Is ethnicity associated with morphine's side effects in children? Morphine pharmacokinetics, analgesic response, and side effects in children having tonsillectomy.
abstract: OBJECTIVE
  To examine whether morphine pharmacokinetics (PK) and/or genetic polymorphisms in opioid-related genes, underlie differences in analgesic response and side effects to morphine in Latino (L) vs non-Latino Caucasian (NL) children.
  
  
  BACKGROUND
  Morphine has high interindividual variability in its analgesic response and side effects profile. Earlier studies suggest that morphine response may vary by race and ethnicity.
  
  
  METHODS
  Prospective cohort study in L and NL children, 3-17 years of age comparing pain scores, occurrence of side effects, plasma morphine, morphine-6- and morphine-3-glucuronide concentrations measured after a single morphine IV bolus administration. Noncompartmental pharmacokinetic analysis and genotyping for 28 polymorphisms in eight genes (UGT1A8, UGT2B7, ABCB1, COMT, STAT6, MC1R, OPRM1, and ARRB2) were performed.
  
  
  RESULTS
  We enrolled 68 children (33 L, 35 NL). There were no differences in pain scores or need for rescue analgesia. Statistically significant differences in the occurrence of side effects were documented: While 58% of L children experienced at least one side effect only 20% of NL did (P = 0.001). Pruritus was four times (P = 0.006) and emesis seven times (P = 0.025) more frequent in L compared with NL. PK parameters were similar between groups. None of the assessed polymorphisms mediated the association between ethnicity and side effects.
  
  
  CONCLUSIONS
  We found statistically significant differences in the occurrence of side effects after morphine administration between L and NL children. Neither differences in morphine or metabolite concentrations, nor the genetic polymorphisms examined explain these findings. Studies are needed to further investigate reasons for the increase in morphine side effects by Latino ethnicity.
authors.affiliation: Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA. nathalia.jimenez@seattlechildrens.org
authors.forename: Nathalia
authors.initials: N
authors.lastname: Jimenez
authors.forename: Gail D
authors.initials: GD
authors.lastname: Anderson
authors.forename: Danny D
authors.initials: DD
authors.lastname: Shen
authors.forename: Susan S
authors.initials: SS
authors.lastname: Nielsen
authors.forename: Federico M
authors.initials: FM
authors.lastname: Farin
authors.forename: Kristy
authors.initials: K
authors.lastname: Seidel
authors.forename: Anne M
authors.initials: AM
authors.lastname: Lynn
mesh_terms: D000233:Adenoidectomy / Q000009:adverse effects; D000293:Adolescent; D000701:Analgesics, Opioid / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004798:Enzymes / Q000235:genetics / Q000378:metabolism; D005006:Ethnicity / Q000235:genetics / Q000706:statistics & numerical data*; D005260:Female; D005838:Genotype; D006630:Hispanic or Latino; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D009020:Morphine / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D010147:Pain Measurement / Q000187:drug effects; D010149:Postoperative Pain / Q000188:drug therapy*; D011110:Polymorphism, Genetic / Q000235:genetics; D011446:Prospective Studies; D011537:Pruritus / Q000139:chemically induced / Q000453:epidemiology; D011957:Receptors, Opioid / Q000235:genetics / Q000378:metabolism; D014068:Tonsillectomy / Q000009:adverse effects*; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced / Q000453:epidemiology; D044465:White People
chemical_list: D000701:Analgesics, Opioid; D004798:Enzymes; D011957:Receptors, Opioid; D009020:Morphine