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Effect of genetic polymorphisms in UDP-glucuronosyltransferase 1A6 (UGT1A6) on acetylsalicylic acid metabolism in healthy female volunteers. | LitMetric

AI Article Synopsis

  • - The study aimed to evaluate how genetic variations in the UGT1A6 gene affect the metabolism of acetylsalicylic acid (ASA) and its metabolites in female participants.
  • - Nine female participants with two different UGT1A6 genotypes were given ASA, and blood samples were taken to measure the levels of ASA and its metabolites over 10 hours using a HPLC method.
  • - Results showed significant differences in the pharmacokinetics of salicylic acid (SA) between the two genotypes, with UGT1A6*2 homozygotes exhibiting lower plasma levels, suggesting faster drug metabolism compared to UGT1A6*1 homozygotes.

Article 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.

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.

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Source
http://dx.doi.org/10.1159/000205824DOI Listing

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