Determinants of Aspirin Metabolism in Healthy Men and Women: Effects of Dietary Inducers of UDP-Glucuronosyltransferases

作者：Navarro Sandi L; Saracino Misty R; Makar Karen W; Thomas Sushma S; Li Lin; Zheng Yingye; Levy Lisa; Schwarz Yvonne; Bigler Jeannette; Potter John D; Lampe Johanna W^*

来源：Journal of Nutrigenetics and Nutrigenomics, 2011, 4(2): 110-118.

DOI：10.1159/000327782

• Aspirin
• Citrus
• Cruciferous vegetables
• Glucuronidation
• Soy
• UDP-glucuronosyltransferases

Background/Aims: 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). Conclusion: Diet may influence the pharmacokinetics of ASA, but effects may be through modulation of glycine conjugation rather than glucuronidation.

• 出版日期2011