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KMID : 0043320190420121101
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Archives of Pharmacal Research
2019 Volume.42 No. 12 p.1101 ~ p.1106
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Effects of steady-state clarithromycin on the pharmacokinetics of zolpidem in healthy subjects
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Lee Choong-Min
Jung Eui-Hyun
Byeon Ji-Yeong
Kim Se-Hyung
Jang Choon-Gon
Lee Yun-Jeong
Lee Seok-Yong
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Abstract
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Zolpidem is extensively metabolized by CYP3A4, CYP2C9 and CYP1A2. Previous studies demonstrated that pharmacokinetics of zolpidem was affected by CYP inhibitors, but not by short-term treatment of clarithromycin. The objective of this study was to investigate the effects of steady-state clarithromycin on the pharmacokinetics of zolpidem in healthy subjects. In the control phase, 33 subjects received a single dose of zolpidem (5 mg). One week later, in the clarithromycin phase, the subjects received clarithromycin (500 mg) twice daily for 5 days to reach steady state concentrations, followed by zolpidem (5 mg) and clarithromycin (500 mg). In each phase, plasma concentrations of zolpidem were evaluated up to 12 h after drug administration by using liquid chromatography-tandem mass spectrometry method. In the clarithromycin phase, mean total area under the curve of zolpidem (AUCinf) was 1.62-fold higher and the time to reach peak plasma concentration of zolpidem (tmax) was prolonged by 1.95-fold compared to the control phase. In addition, elimination half-life (t1/2) of zolpidem was 1.40-fold longer during co-administration with clarithromycin and its apparent oral clearance (CL/F) was 36.2% lower with clarithromycin administration. The experimental data demonstrate the significant pharmacokinetic interaction between zolpidem and clarithromycin at steady-state.
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KEYWORD
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Zolpidem, Clarithromycin, Drug interaction, Pharmacokinetics
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