title: Effect of genetic polymorphisms in UDP-glucuronosyltransferase 1A6 (UGT1A6) on acetylsalicylic acid metabolism in healthy female volunteers.
abstract: OBJECTIVE
  To compare plasma concentrations of acetylsalicylic acid (ASA) and its metabolites between genetic polymorphisms in the gene encoding for UDP-glucuronosyltransferase 1A6 (UGT1A6), an enzyme involved in ASA metabolism.
  
  
  METHODS
  Five UGT1A6*1 and 4 UGT1A6*2 homozygote females were given 320 mg ASA once daily for 8 days. During the first and last day of treatment, several blood samples were taken over a 10-hour time period and analyzed for plasma levels of ASA and its main metabolites salicylic acid (SA) and salicyluric acid (SUA), using a validated HPLC method. The pharmacokinetic data were assessed with the Time Constant Approach and both genotypes were compared using the Mann-Whitney U test.
  
  
  RESULTS
  ASA and SUA showed similar pharmacokinetic parameters in the two UGT1A6 genotypes. However, pharmacokinetic parameters for SA differed significantly: the mean area under the pharmacokinetic curve for the UGT1A6*1 and UGT1A6*2 homozygotes was 136 and 94 microg/ml.h (p = 0.04), and median C(max) was 23 and 17 microg/ml (p = 0.01), respectively.
  
  
  CONCLUSIONS
  In females receiving ASA, the presence of the UGT1A6*2 compared to the UGT1A6*1 homozygote genotype is associated with lower plasma levels of SA, indicating faster pharmacokinetics.
authors.affiliation: Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. M.vanOijen@mdl.umcn.nl
authors.forename: Martijn G H
authors.initials: MG
authors.lastname: van Oijen
authors.forename: Christine
authors.initials: C
authors.lastname: Barthélémy
authors.forename: Marcel J R
authors.initials: MJ
authors.lastname: Janssen
authors.forename: Etienne
authors.initials: E
authors.lastname: Joiris
authors.forename: Wilbert H M
authors.initials: WH
authors.lastname: Peters
authors.forename: Robert J F
authors.initials: RJ
authors.lastname: Laheij
authors.forename: Paul
authors.initials: P
authors.lastname: Smits
authors.forename: Pascal
authors.initials: P
authors.lastname: Odou
authors.forename: Jan B M J
authors.initials: JB
authors.lastname: Jansen
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D001241:Aspirin / Q000097:blood*; D005260:Female; D014453:Glucuronosyltransferase / Q000235:genetics*; D006626:Hippurates / Q000097:blood; D006720:Homozygote; D006801:Humans; D011110:Polymorphism, Genetic; D020156:Salicylic Acid / Q000097:blood; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D006626:Hippurates; C000693:salicylurate; C110655:UDP-glucuronosyltransferase, UGT1A6; D014453:Glucuronosyltransferase; D020156:Salicylic Acid; D001241:Aspirin