Abstract
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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This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and Future Planning (NRF-2016R1A2B4007381 and NRF-2019RIA2C1004582).
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Lee, CM., Jung, E.H., Byeon, JY. et al. Effects of steady-state clarithromycin on the pharmacokinetics of zolpidem in healthy subjects. Arch. Pharm. Res. 42, 1101–1106 (2019). https://doi.org/10.1007/s12272-019-01201-5
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DOI: https://doi.org/10.1007/s12272-019-01201-5