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

CYP3A4*18基因型对唑吡坦在健康回族志愿者体内的药代动力学的影响（英文）

作　　者：吴秀君[1] 郭涛[2] 张凤芹[1] 马然[1] 左金梁[3] 

机构地区：[1]辽宁中医药大学附属医院,辽宁沈阳110032 [2]沈阳军区总医院药剂科,辽宁沈阳110015 [3]天津医科大学药学院,天津300070

出　　处：《Journal of Chinese Pharmaceutical Sciences》2016年第2期122-127,共6页中国药学（英文版）

基　　金：Funds of the Chinese Army Medical Science and Technology Research"Eleventh Five-Year Plan"Project(Grant No.06G023)

摘　　要：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 Cm,x 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 AUC0-1 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 Cmax and AUC0-1 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.本研究旨在研究CYP3A4*18基因型对唑吡坦在健康回族人体内的药代动力学行为的影响。采用多聚酶链反应.限制性片段(PCR-RELP)分析,检测200名健康回族志愿者的CYP3A4*18等位基因。根据CYP3A4*18等位基因筛选结果,选择CYP3A4*1/*1,CYP3A4*1/*18和CYP3A4*18/*18携带者各6名,单剂量口服给予10 mg酒石酸唑吡坦片,分别于给药前和给药后不同时间点采集血浆样品。使用HPLC-FLD法测定唑吡坦血药浓度,采用DAS2.0软件计算药代动力学参数,并采用SPSS17.0软件进行统计分析。结果显示不同基因型受试者唑吡坦的药代动力学行为有明显差异。杂合突变组(*1/*18)和纯合突变组(*18/*18)的唑吡坦C_(max)分别为野生组(*1/*1)的0.89(95%CI:0.65-1.12)和0.57(95%CI:0.47-0.66);AUC_(0-t)分别为*1/*1组的0.74(95%CI:0.22-1.26)和0.61(95%CI:0.24-0.98)。唑吡坦药代动力学参数呈现明显的基因.剂量效应(P<0.05)。本研究证明CYP3A4*18等位基因增强了CYP3A4对唑吡坦的代谢水平,对唑吡坦的人体内药代动力学行为有显著影响。

关 键 词：ZOLPIDEM CYP3A4＊ 18 PHARMACOKINETICS Chinese Hui 

分 类 号：R969.1[医药卫生—药理学]