CYP2C9 and OATP1B1 genetic polymorphisms affect the metabolism and transport of glimepiride and gliclazide

Scientific Reports
Fayou YangChunhua Xia

Abstract

The therapeutic use of glimepiride and gliclazide shows substantial inter-individual variation in pharmacokinetics and pharmacodynamics in human populations, which might be caused by genetic differences among individuals. The aim of this study was to assess the effect of CYP2C9 and OATP1B1 genetic polymorphisms on the metabolism and transport of glimepiride and gliclazide. The uptake of glimepiride and gliclazide was measured in OATP1B1*1a, *5 and *15-HEK293T cells, and their metabolism was measured using CYP2C9*1, *2 and *3 recombinase by LC-MS. Glimepiride in OATP1B1*1a, *5 and *15-HEK293T cells had Vmax values of 155 ± 18.7, 80 ± 9.6, and 84.5 ± 8.2 pmol/min/mg, while gliclazide had Vmax values of 15.7 ± 4.6, 7.2 ± 2.5, and 8.7 ± 2.4 pmol/min/mg, respectively. The clearance of glimepiride and gliclazide in OATP1B1*5 and *15 was significantly reduced compared to the wild-type. Glimepiride in the presence of CYP2C9*1, *2 and *3 recombinase had Vmax values of 21.58 ± 7.78, 15.69 ± 5.59, and 9.17 ± 3.03 nmol/min/mg protein, while gliclazide had Vmax values of 15.73 ± 3.11, 10.53 ± 4.06, and 6.21 ± 2.94 nmol/min/mg protein, respectively. The clearance of glimepiride and gliclazide in CYP2C9*2 and *3 was significantly reduced comp...Continue Reading

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Citations

Mar 21, 2020·Drug Metabolism and Disposition : the Biological Fate of Chemicals·James C FuscoeQiang Shi
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Jul 31, 2021·Biopharmaceutics & Drug Disposition·Jeffry Adiwidjaja, Lucy Sasongko
Oct 6, 2021·Diabetes Care·Adem Y DawedUNKNOWN MetGen Plus investigators:

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Methods Mentioned

BETA
Protein Assay

Software Mentioned

Prism
Image Lab
GraphPad Prism
SPSS
GraphPad

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