The influences of CYP2C9*1/*3 genotype on the pharmacokinetics of zolpidem.
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Byeon JY, Kim YH, Kim SH, Lee CM, Jung EH, Chae WK, Jang CG, Lee SY, Lee YJ
The influences of CYP2C9*1/*3 genotype on the pharmacokinetics of zolpidem.
Arch Pharm Res. 2018 Sep;41(9):931-936. doi: 10.1007/s12272-018-1070-y. Epub 2018 Sep 3.
- PubMed ID
- 30178440 [ View in PubMed]
- Abstract
Zolpidem is predominantly metabolized by CYP3A4, and to a lesser extent by CYP2C9, CYP1A2, CYP2D6 and CYP2C19. The aim of this study was to identify the effects of CYP2C9*3 allele on the pharmacokinetics of zolpidem. Healthy male subjects were divided into two genotype groups, CYP2C9*1/*1 and CYP2C9*1/*3. They received a single oral dose of 5 mg zolpidem, and the plasma concentrations of zolpidem were determined up to 12 h after drug administration. In addition, since zolpidem is metabolized at a high rate by CYP3A4, the effect of CYP2C9*3 allele on the pharmacokinetics of zolpidem was also observed in the condition where CYP3A4 was sufficiently inhibited by the steady-state concentration of clarithromycin, a potent CYP3A4 inhibitor. For this, clarithromycin 500 mg was administered twice daily for 5 days. Plasma concentrations of zolpidem were determined using liquid chromatography-tandem mass spectrometry method. The overall pharmacokinetic parameters of zolpidem were not significantly different between two CYP2C9 genotypes. Even with the potent CYP3A4 inhibitor clarithromycin present at steady-state concentrations, there were no significant differences in the exposure of zolpidem, except for elimination half-life (t1/2). In conclusion, our study suggests that CYP2C9*1/*3 genotype does not affect the plasma exposure of zolpidem.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Zolpidem Cytochrome P450 2C19 Protein Humans UnknownSubstrateDetails Zolpidem Cytochrome P450 2C9 Protein Humans UnknownSubstrateDetails Zolpidem Cytochrome P450 2D6 Protein Humans UnknownSubstrateDetails