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KMID : 0043320200430090976
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Archives of Pharmacal Research
2020 Volume.43 No. 9 p.976 ~ p.981
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Relationship between plasma exposure of zolpidem and CYP2D6 genotype in healthy Korean subjects
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Jung Eui-Hyun
Lee Choong-Min
Byeon Ji-Yeong
Shin Hyo-Bin
Oh Kyung-Yul
Cho Chang-Keun
Lim Chang-Woo
Jang Choon-Gon
Lee Seok-Yong
Lee Yun-Jeong
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Abstract
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Zolpidem, a widely prescribed hypnotic agent, is extensively metabolized by cytochrome P450 (CYP) 3A4, and CYP2C9, CYP1A2 and CYP2D6 are also involved in the metabolism of zolpidem. The aim of the study was to investigate the effects of CYP2D6 genotypes on the exposure of zolpidem. The healthy male volunteers were divided into three different genotype groups (CYP2D6*wt/*wt [*wt?=?*1 or *2], CYP2D6*wt/*10, and CYP2D6*10/*10). Each subject received a single oral dose of zolpidem 5 mg with or without a steady-state concentration of clarithromycin (a potent inhibitor of CYP3A4), and plasma concentrations of zolpidem were measured up to 12 h after zolpidem dosing by using liquid chromatography-tandem mass spectrometry method. When zolpidem was administered alone, the exposure of zolpidem (the total areas under the curve and the mean peak plasma concentrations) was not significantly different among three different genotype groups. Even with the steady-state concentration of clarithromycin, a potent CYP3A4 inhibitor, there were no significant differences in the exposure of zolpidem in relation to CYP2D6 genotypes.
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KEYWORD
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Zolpidem, CYP2D6, Genotype, Polymorphisms, Pharmacokinetics
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