Effect of CYP3A4 genetic polymorphisms on pharmacokinetics of tinidazole  

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

作　　者：Xinyu Chang Tao Guo Guiming Guo 常馨予;郭涛;郭桂明(首都医科大学附属北京中医医院临床药学科,北京100010;沈阳军区总医院药剂科,辽宁沈阳110016)

机构地区：[1]Department of Clinical Pharmacy,Beijing Traditional Chinese Medicine Hospital Capital Medical University,Beijingl00038,China [2]Department of Pharmacy,the General Hospital of Shenyang Military Region,Shenyang 110015,China

出　　处：《Journal of Chinese Pharmaceutical Sciences》2020年第4期272-279,共8页中国药学（英文版）

基　　金：The Research Grant from the 115 Project of Legionary Medical Treatment and Public Health(Grant No.06G023).

摘　　要：In the present study, we aimed to investigate the frequency of CYP3 A4*18 B genetic polymorphism in Han Chinese populations, and to assess the effect of the CYP3 A4*18 B 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 CYP3 A4*18 B. A pharmacokinetic study of tinidazole was then carried out in two groups with CYP3 A4*1/*1(n = 10) and CYP3 A4*1/*18 B(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 CYP3 A4*1/*1 genotype, and 12 were found with CYP3 A4*1/*18 B genotype. CYP3 A4*18 B/*18 B were absent from all subjects. The allele frequencies of CYP3 A4*18 B were 6%. The pharmacokinetic parameters of CYP3 A4*1/*1 genotype and CYP3 A4*1/*18 B genotype in healthy subjects were as follows: t1/2:(15.92±1.62),(15.77±1.67) h;Cmax:(18.72±3.10),(20.25±3.42) mg/L;tmax:(1.50±0.66),(1.45±0.69) h;Vd/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 CYP3 A4*18 B genetic polymorphism did not affect pharmacokinetics of tinidazolein healthy volunteers.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72h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:t1/2:(15.92±1.62),(15.77±1.67)h;Cmax:(18.72±3.10),(20.25±3.42)mg/L;tmax:(1.50±0.66),(1.45±0.69)h;Vd/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：TINIDAZOLE CYP3A4 PHARMACOKINETICS 

分 类 号：R945[医药卫生—微生物与生化药学]