摘要
目的研究中国健康人CYP2B6*6基因多态性对依法韦仑药动学的影响。方法应用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)将40名健康中国志愿者分为3组:CYP2B6*1/*1组(n=29),CYP2B6*1/*6组(n=8)和CYP2B6*6/*6组(n=3)。受试者单剂量口服依法韦仑600 mg,收集给药后336 h内的一系列血样,用HPLC-MS/MS法测定依法韦仑的血药浓度并进行药动学分析。结果与CYP2B6*1/*1组相比,CYP2B6*6/*6基因型的志愿者的依法韦仑血药浓度较高(P<0.05);CYP2B6*1/*6组与CYP2B6*6/*6组的主要药动学参数(t1/2、AUC0-336 h和AUC0-∞)均存在显著差异(P<0.05或P<0.01);CYP2B6*1/*6组与CYP2B6*6/*6组的tmax和ρmax无显著差异(P>0.05)。结论 CYP2B6*6等位基因突变能引起代谢表型的改变,影响依法韦仑在中国健康人群的代谢。根据基因型制定个体化给药方案有助于依法韦仑的合理使用。
AIM To investigate the influence of CYP2B6＊6 polymorphism on pharmacokinetics of efavirenz in Chinese healthy people. METHODS Totally 40 healthy Chinese volunteers were separated into three groups by the polymerase chain reaction and restriction fragment length polymorphism（ PCR- RFLP） ：CYP2B6＊1/＊1 group（n = 29）, CYP2B6＊1/＊6 group（n = 8） and CYP2B6＊6/＊6 group（n = 3）. After administration of a single oral dose of efavirenz 600 mg, plasma drug concentration during 336 h was measured by HPLC- MS/MS and the pharmacokinetic analysis was done. RESULTS Compared with CYP2B6 ＊1/＊1 group,volunteers with CYP2B6 ＊6/＊6 showed higher efavirenz plasma concentrations（ P〈0.05）; the mean pharma-cokinetic parameters including t1 / 2, AUC0-336 hand AUC0-∞of efavirenz had significant differences between CYP2B6＊1/＊6 group and CYP2B6＊6/＊6 group（P〈0.05 or P〈0.01）; tmaxand ρmaxin CYP2B6＊1/＊6 group and CYP2B6 ＊6/＊6 group had no significant differences（ P〉0.05）. CONCLUSION The allelic gene mutation of CYP2B6 ＊6 can cause the changes of metabolic phenotype and have effects on the metabolism of efavirenz in Chinese healthy people. Individualized dose regimen of efavirenz based on identification of genotype, can be of great benefit to the reasonable use of it.
出处
《中国新药与临床杂志》
CAS
CSCD
北大核心
2016年第2期131-137,共7页
Chinese Journal of New Drugs and Clinical Remedies
基金
Medical science and technology project of He-nan(201303174)
关键词
依法韦仑
细胞色素P450
CYP2B6
基因多态性
色谱法
高压液相
串联质谱法
药动学
efavirenz
cytochrome P-450 CYP2B6
gene polymorphisms
chromatography
high performance liquid chromatography
tandem mass spectrometry
pharmacokinetics
作者简介
[Biography] WANG Pei, female, postgraduate, be engaged in pharmacology, E-mail： wpzz0709@sina.cn
[Correspondence author] ZHANG Li-rong, Phn： 86-371-6778-1855, E-mail： lrzhang@zzu.edu.cn; LI Xiao-tian, E-mail： lixt@zzu.edu.cn
