title: Determinants of aspirin metabolism in healthy men and women: effects of dietary inducers of UDP-glucuronosyltransferases.
abstract: OBJECTIVE
  Interindividual variation in aspirin (ASA) metabolism is attributed to concomitant use of drugs or alcohol, urine pH, ethnicity, sex, and genetic variants in UDP-glucuronosyltransferases (UGT). Little is known about the effects of diet.
  
  
  METHODS
  We evaluated cross-sectionally whether urinary excretion of ASA and its metabolites [salicylic acid (SA), salicyluric acid (SUA) phenolic glucuronide (SUAPG), salicylic acid acyl glucuronide (SAAG) and salicylic acid phenolic glucuronide (SAPG)] differed by UGT1A6 genotype and dietary factors shown to induce UGT. Following oral treatment with 650 mg ASA, urine was collected over 8 h in 264 men and 264 women (21-45 years old).
  
  
  RESULTS
  There were statistically significant differences in metabolites excreted between sexes and ethnicities. Men excreted more SUA; women more ASA (p = 0.03), SA, SAAG and SAPG (p ≤ 0.001 for all). Compared to Caucasians, Asians excreted more ASA, SA and SAAG, and less SUA and SUAPG (p ≤ 0.03 for all); African-Americans excreted more SAAG and SAPG and less SUA (p ≤ 0.04). There was no effect of UGT1A6 genotypes. Increased ASA and decreased SUAPG excretion was observed with increased servings of vegetables (p = 0.008), specifically crucifers (p = 0.05).
  
  
  CONCLUSIONS
  Diet may influence the pharmacokinetics of ASA, but effects may be through modulation of glycine conjugation rather than glucuronidation.
authors.affiliation: Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Wash., USA.
authors.forename: Sandi L
authors.initials: SL
authors.lastname: Navarro
authors.forename: Misty R
authors.initials: MR
authors.lastname: Saracino
authors.forename: Karen W
authors.initials: KW
authors.lastname: Makar
authors.forename: Sushma S
authors.initials: SS
authors.lastname: Thomas
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.forename: Yingye
authors.initials: Y
authors.lastname: Zheng
authors.forename: Lisa
authors.initials: L
authors.lastname: Levy
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Schwarz
authors.forename: Jeannette
authors.initials: J
authors.lastname: Bigler
authors.forename: John D
authors.initials: JD
authors.lastname: Potter
authors.forename: Johanna W
authors.initials: JW
authors.lastname: Lampe
mesh_terms: D000328:Adult; D001241:Aspirin / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D003430:Cross-Sectional Studies; D004032:Diet; D004790:Enzyme Induction; D005006:Ethnicity; D005260:Female; D056726:Genetic Association Studies; D020719:Glucuronides / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000096:biosynthesis* / Q000235:genetics; D005998:Glycine / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D054647:Nutrigenomics; D012727:Sex Characteristics; D055815:Young Adult
chemical_list: D020719:Glucuronides; C110655:UDP-glucuronosyltransferase, UGT1A6; D014453:Glucuronosyltransferase; D001241:Aspirin; D005998:Glycine