CYP3A4基因多态性对健康受试者体内替硝唑药代动力学的影响

doi:10.5246/jcps.2020.04.026

中国药学(英文版) ›› 2020, Vol. 29 ›› Issue (4): 272-279.DOI: 10.5246/jcps.2020.04.026

CYP3A4基因多态性对健康受试者体内替硝唑药代动力学的影响

常馨予^1*, 郭涛², 郭桂明¹

1. 首都医科大学附属北京中医医院临床药学科, 北京 100010
2. 沈阳军区总医院药剂科, 辽宁沈阳 110016

收稿日期:2019-11-25 修回日期:2019-12-06 出版日期:2020-04-30 发布日期:2020-01-10
通讯作者: Tel.: +86-10-52177321, E-mail: xinyu_chang@163.com
基金资助:
The Research Grant from the 115 Project of Legionary Medical Treatment and Public Health (Grant No. 06G023).

Effect of CYP3A4 genetic polymorphisms on pharmacokinetics of tinidazole

Xinyu Chang^1*, Tao Guo², Guiming Guo¹

1. Department of Clinical Pharmacy, Beijing Traditional Chinese Medicine Hospital, Capital Medical University, Beijing100038, China
2. Department of Pharmacy, the General Hospital of Shenyang Military Region, Shenyang 110015, China

Received:2019-11-25 Revised:2019-12-06 Online:2020-04-30 Published:2020-01-10
Contact: Tel.: +86-10-52177321, E-mail: xinyu_chang@163.com
Supported by:
The Research Grant from the 115 Project of Legionary Medical Treatment and Public Health (Grant No. 06G023).

摘要/Abstract

摘要：

研究中国汉族人群CYP3A4*18B基因多态性的频率, 并探讨CYP3A4*18B基因多态性对替硝唑药代动力学的影响。本研究共招募100名来自中国汉族的健康志愿者, 采用PCR-RFLP方法检测CYP3A4*18B的基因多态性。选择CYP3A4*1/*1 (n = 10)野生型受试者和CYP3A4*1/*18B (n = 9)突变杂合型受试者进行替硝唑的药代动力学研究。单剂量口服替硝唑片剂后采集72 h内的血样, 使用高效液相色谱法测定血浆样本中替硝唑的浓度。发现88名健康志愿者携带CYP3A4*1/*1基因型, 12人携带CYP3A4*1/*18B基因型, 未发现携带CYP3A4*18B/*18B基因型。CYP3A4*18B等位基因频率为6%。CYP3A4*1/*1基因型和CYP3A4*1/*18B基因型受试者体内的药动学参数分别为: t_1/2: (15.92±1.62), (15.77±1.67) h; C_ma_x: (18.72±3.10), (20.25±3.42) mg/L; t_max: (1.50±0.66), (1.45±0.69) h; V_d/F: (55.73±10.66), (51.30±7.75) L; CL/F: (2.44±0.47),(2.26±0.30) L·h; AUC₀_–_∞: (424.40±82.38), (450.53±69.48) mg·h/L。研究发现CYP3A4*18B基因多态性对替硝唑健康志愿者的药代动力学无明显影响。

关键词: 替硝唑, CYP3A4, 药动学

Abstract:

In the present study, we aimed to investigate the frequency of CYP3A4*18B genetic polymorphism in Han Chinese populations, and to assess the effect of the CYP3A4*18B genetic polymorphism on the pharmacokinetics of tinidazole. A total of 100 healthy volunteers from Han nationalities in China were recruited. DNA was extracted from peripheral leukocytes using a standard protocol. A PCR-RFLP method was developed to detect the alleles of CYP3A4*18B. A pharmacokinetic study of tinidazole was then carried out in two groups with CYP3A4*1/*1 (n = 10) and CYP3A4*1/*18B (n = 9) genotypes. Concentrations of tinidazole were determined using high-performance liquid chromatography in plasma samples that were collected up to 72 h after drug intake. In this study, 88 healthy volunteers were found with CYP3A4*1/*1 genotype, and 12 were found with CYP3A4*1/*18Bgenotype. CYP3A4*18B/*18B were absent from all subjects. The allele frequencies of CYP3A4*18B were 6%. The pharmacokinetic parameters of CYP3A4*1/*1 genotype and CYP3A4*1/*18B genotype in healthy subjects were as follows: t_1/2: (15.92±1.62), (15.77±1.67) h; C_max: (18.72±3.10), (20.25±3.42) mg/L; t_max: (1.50±0.66), (1.45±0.69) h; V_d/F: (55.73±10.66), (51.30±7.75) L; CL/F: (2.44±0.47), (2.26±0.30) L·h; AUC₀_–_∞: (424.40±82.38), (450.53±69.48) mg·h/L. Collectively, the CYP3A4*18B genetic polymorphism did not affect pharmacokinetics of tinidazolein healthy volunteers.

Key words: Tinidazole, CYP3A4, Pharmacokinetics

中图分类号:

R945

Supporting:

常馨予, 郭涛, 郭桂明. CYP3A4基因多态性对健康受试者体内替硝唑药代动力学的影响[J]. 中国药学(英文版), 2020, 29(4): 272-279.

Xinyu Chang, Tao Guo, Guiming Guo . Effect of CYP3A4 genetic polymorphisms on pharmacokinetics of tinidazole[J]. Journal of Chinese Pharmaceutical Sciences, 2020, 29(4): 272-279.

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CYP3A4基因多态性对健康受试者体内替硝唑药代动力学的影响

Effect of CYP3A4 genetic polymorphisms on pharmacokinetics of tinidazole

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