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
School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
College of Pharmacy, Dankook University, Cheonan, 31116, Republic of Korea.
Arch Pharm Res. 2020 Sep;43(9):976-981. doi: 10.1007/s12272-020-01250-1. Epub 2020 Jul 13.
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], CYP2D6wt/10, and CYP2D610/*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.
唑吡坦是一种广泛使用的催眠药物，主要通过细胞色素P450（CYP）3A4进行广泛代谢，CYP2C9、CYP1A2和CYP2D6也参与唑吡坦的代谢。本研究的目的是调查CYP2D6基因多态性对唑吡坦暴露量的影响。健康男性志愿者被分为三个不同的基因型组（CYP2D6*wt/*wt[wt = 1或2]、CYP2D6wt/10和CYP2D610/*10）。每位受试者口服单剂量5 mg唑吡坦，同时或不同时给予稳态浓度的克拉霉素（一种强效CYP3A4抑制剂），并采用液相色谱-串联质谱法在给药后12小时内测定血浆中唑吡坦的浓度。单独给予唑吡坦时，三种不同基因型组之间唑吡坦的暴露量（曲线下总面积和平均血浆峰浓度）无显著差异。即使给予强效CYP3A4抑制剂克拉霉素的稳态浓度，唑吡坦的暴露量在不同CYP2D6基因型之间也无显著差异。
