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Relationship between plasma exposure of zolpidem and CYP2D6 genotype in healthy Korean subjects

Archives of Pharmacal Research 2020년 43권 9호 p.976 ~ 981
정의현, 이중민, 변지영, 신효빈, 오경열, 조창근, 임창우, 장춘곤, 이석용, 이윤정,
소속 상세정보
정의현 ( Jung Eui-Hyun ) - Sungkyunkwan University School of Pharmacy
이중민 ( Lee Choong-Min ) - Sungkyunkwan University School of Pharmacy
변지영 ( Byeon Ji-Yeong ) - Sungkyunkwan University School of Pharmacy
신효빈 ( Shin Hyo-Bin ) - Sungkyunkwan University School of Pharmacy
오경열 ( Oh Kyung-Yul ) - Sungkyunkwan University School of Pharmacy
조창근 ( Cho Chang-Keun ) - Sungkyunkwan University School of Pharmacy
임창우 ( Lim Chang-Woo ) - Sungkyunkwan University School of Pharmacy
장춘곤 ( Jang Choon-Gon ) - Sungkyunkwan University School of Pharmacy
이석용 ( Lee Seok-Yong ) - Sungkyunkwan University School of Pharmacy
이윤정 ( Lee Yun-Jeong ) - Dankook University College of Pharmacy

Abstract


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.

키워드

Zolpidem; CYP2D6; Genotype; Polymorphisms; Pharmacokinetics

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