Effect of CYP3A4*18 genotype on the pharmacokinetics of zolpidem in healthy Chinese Hui subjects

doi:10.5246/jcps.2016.02.013

Abstract

Abstract:

In the present study, we aimed to investigate the effect of CYP3A4*18 genotype on the pharmacokinetics of zolpidem in healthy Chinese Hui volunteers.Blood samples were collected from volunteers for CYP3A4 genotyping using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. A pharmacokinetic study was then carried out in three groups with CYP3A4*1/*1 (n = 6), CYP3A4*1/*18 (n = 6) and CYP3A4*18/*18 (n = 6) genotypes. Plasma levels of zolpidem were determined by HPLC-FLD method before and after a single oral dose of 10 mg zolpidem tartrate tablet. Significant differences were observed in the pharmacokinetic parameters of zolpidem among the three genotype groups (P<0.05). Compared with the CYP3A4*1/*1 group, the C_max of zolpidem in *1/*18 and *18/*18 groups (mean, 95% CI) was 0.89 (0.65–1.12) and 0.57 (0.47–0.66), respectively, and the AUC₀_–_t in the *1/*18 and *18/*18 groups (mean, 95% CI) was 0.74 (0.22–1.26) and 0.61 (0.24–0.98), respectively. There was a significant trend towards lower C_maxand AUC₀_–_t values of zolpidem in individuals with more CYP3A*18 alleles, suggesting a gene-dosage effect.The study demonstrated that the CYP3A4*18 allele played an important role in the pharmacokinetics of the zolpidem after oral administration.

Key words: Zolpidem, CYP3A4*18, Pharmacokinetics, Chinese Hui

CLC Number:

R969.1

Supporting:

Xiujun Wu, Tao Guo, Fengqin Zhang, Ran Ma, Jinliang Zuo. Effect of CYP3A4*18 genotype on the pharmacokinetics of zolpidem in healthy Chinese Hui subjects[J]. Journal of Chinese Pharmaceutical Sciences, 2016, 25(2): 122-127.

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