Effect of genetic polymorphisms in UDP-glucuronosyltransferase 1A6 (UGT1A6) on acetylsalicylic acid metabolism in healthy female volunteers.
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.
van Oijen
Martijn G H
MG
Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. M.vanOijen@mdl.umcn.nl
Barthélémy
Christine
C
Janssen
Marcel J R
MJ
Joiris
Etienne
E
Peters
Wilbert H M
WH
Laheij
Robert J F
RJ
Smits
Paul
P
Odou
Pascal
P
Jansen
Jan B M J
JB
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
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006626:Hippurates; C000693:salicylurate; C110655:UDP-glucuronosyltransferase, UGT1A6; D014453:Glucuronosyltransferase; D020156:Salicylic Acid; D001241:Aspirin