TY - JOUR
T1 - Effect of Genetic Polymorphisms in UDP-Glucuronosyltransferase 1A6 (UGT1A6) on Acetylsalicylic Acid Metabolism in Healthy Female Volunteers
AU - van Oijen, Martijn G. H.
AU - Barthélémy, Christine
AU - Janssen, Marcel J. R.
AU - Joiris, Etienne
AU - Peters, Wilbert H. M.
AU - Laheij, Robert J. F.
AU - Smits, Paul
AU - Odou, Pascal
AU - Jansen, Jan B. M. J.
PY - 2009
Y1 - 2009
N2 - 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 mu g/ml.h ( p = 0.04), and median C(max) was 23 and 17 mu g/ml (p = 0.01), respectively. Conclusion: 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. Copyright (C) 2009 S. Karger AG, Basel
AB - 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 mu g/ml.h ( p = 0.04), and median C(max) was 23 and 17 mu g/ml (p = 0.01), respectively. Conclusion: 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. Copyright (C) 2009 S. Karger AG, Basel
U2 - https://doi.org/10.1159/000205824
DO - https://doi.org/10.1159/000205824
M3 - Article
C2 - 19262071
SN - 0031-7012
VL - 83
SP - 237
EP - 242
JO - Pharmacology
JF - Pharmacology
IS - 4
ER -