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KMID : 0043320220450020114
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Archives of Pharmacal Research
2022 Volume.45 No. 2 p.114 ~ p.121
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Effects of CYP2C9*3 and *13 alleles on the pharmacokinetics and pharmacodynamics of glipizide in healthy Korean subjects
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Kim Nam-Tae
Cho Chang-Keun
Kang Pu-Reum
Park Hye-Jung
Lee Yun-Jeong
Bae Jung-Woo
Jang Choon-Gon
Lee Seok-Yong
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Abstract
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Glipizide is a second-generation sulfonylurea antidiabetic drug. It is principally metabolized to inactive metabolites by genetically polymorphic CYP2C9 enzyme. In this study, we investigated the effects of CYP2C9*3 and *13 variant alleles on the pharmacokinetics and pharmacodynamics of glipizide. Twenty-four healthy Korean volunteers (11 subjects with CYP2C9*1/*1, 8 subjects with CYP2C9*1/*3, and 5 subjects with CYP2C9*1/*13) were recruited for this study. They were administered a single oral dose of glipizide 5 mg. The plasma concentration of glipizide was quantified for pharmacokinetic analysis and plasma glucose and insulin concentrations were measured as pharmacodynamic parameters. The results represented that CYP2C9*3 and *13 alleles significantly affected the pharmacokinetics of glipizide. In subjects with CYP2C9*1/*3 and CYP2C9*1/*13 genotypes, the mean AUC0?∞ were increased by 44.8% and 58.2%, respectively (both P?
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KEYWORD
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Glipizide, CYP2C9, Genetic polymorphism, Genotype, Pharmacokinetics, Pharmacodynamics
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