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KMID : 0043320180410090931
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Archives of Pharmacal Research
2018 Volume.41 No. 9 p.931 ~ p.936
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The influences of CYP2C9*1/*3 genotype on the pharmacokinetics of zolpidem
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Byeon Ji-Yeong
Kim Young-Hoon
Kim Se-Hyung
Lee Choong-Min
Jung Eui-Hyun
Chae Won-Ki
Jang Choon-Gon
Lee Seok-Yong
Lee Yun-Jeong
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Abstract
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Zolpidem is predominantly metabolized by CYP3A4, and to a lesser extent by CYP2C9, CYP1A2, CYP2D6 and CYP2C19. The aim of this study was to identify the effects of CYP2C9*3 allele on the pharmacokinetics of zolpidem. Healthy male subjects were divided into two genotype groups, CYP2C9*1/*1 and CYP2C9*1/*3. They received a single oral dose of 5 mg zolpidem, and the plasma concentrations of zolpidem were determined up to 12 h after drug administration. In addition, since zolpidem is metabolized at a high rate by CYP3A4, the effect of CYP2C9*3 allele on the pharmacokinetics of zolpidem was also observed in the condition where CYP3A4 was sufficiently inhibited by the steady-state concentration of clarithromycin, a potent CYP3A4 inhibitor. For this, clarithromycin 500 mg was administered twice daily for 5 days. Plasma concentrations of zolpidem were determined using liquid chromatography-tandem mass spectrometry method. The overall pharmacokinetic parameters of zolpidem were not significantly different between two CYP2C9 genotypes. Even with the potent CYP3A4 inhibitor clarithromycin present at steady-state concentrations, there were no significant differences in the exposure of zolpidem, except for elimination half-life (t1/2). In conclusion, our study suggests that CYP2C9*1/*3 genotype does not affect the plasma exposure of zolpidem.
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KEYWORD
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Zolpidem, CYP2C9, Genetic polymorphism, Pharmacokinetics
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