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KMID : 0043320230460050438
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Archives of Pharmacal Research
2023 Volume.46 No. 5 p.438 ~ p.447
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Effects of CYP2C9 and CYP2C19 genetic polymorphisms on the pharmacokinetics and pharmacodynamics of gliclazide in healthy subjects
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Kang Pu-Reum
Cho Chang-Keun
Jang Choon-Gon
Lee Seok-Yong
Lee Yun-Jeong
Choi Chang-Ik
Bae Jung-Woo
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Abstract
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Gliclazide metabolism is mediated by genetically polymorphic CYP2C9 and CYP2C19 enzymes. We investigated the effects of CYP2C9 and CYP2C19 genetic polymorphisms on the pharmacokinetics and pharmacodynamics of gliclazide. Twenty-seven Korean healthy volunteers were administered a single oral dose of gliclazide 80 mg. The plasma concentration of gliclazide was quantified for the pharmacokinetic analysis and plasma concentrations of glucose and insulin were measured as pharmacodynamic parameters. The pharmacokinetics of gliclazide showed a significant difference according to the number of defective alleles of combined CYP2C9 and CYP2C19. The two defective alleles group (group 3) and one defective allele group (group 2) showed 2.34- and 1.46-fold higher AUC0?∞ (P?
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KEYWORD
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Gliclazide, CYP2C9, CYP2C19, Genetic polymorphism, Pharmacokinetics, Pharmacodynamics
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