POR*28对硝苯地平在健康受试者体内药动学的影响  

Effect of POR*28 gene polymorphism on pharmacokinetics of nifedipine in Chinese healthy volunteers

作　　者：王爱凤[1] 齐艳霞[1] 闫良[2] 张莉蓉[2] 秦玉花[1] 

机构地区：[1]河南省人民医院药学部,河南郑州450003 [2]郑州大学基础医学院药理学教研室,河南郑州450001

出　　处：《中国医院药学杂志》2014年第11期898-901,共4页Chinese Journal of Hospital Pharmacy

基　　金：2013年度河南省医学科技攻关计划普通项目(编号:201303174)

摘　　要：目的:探讨细胞色素P450氧化还原酶(POR)*28基因多态性对硝苯地平在健康人体内药动学的影响。方法:在45名中国汉族健康受试者中,用PCR产物直接测序法检测POR*28基因型,POR*28 CC、CT和TT3种基因型分别为15,24和6例,分别在单次服用90 mg硝苯地平后用高效液相色谱-质谱联用法分析受试者的硝苯地平血药浓度。用3P97软件计算药动学参数。结果:单次给予硝苯地平时的药时曲线下面积(AUC0-∞)、清除率(CL/F)和半衰期(t1/2)在POR*283种基因型个体间均具有显著性差异(P<0.05)。而TT组的最大血药浓度(Cmax)和达峰时间(tmax)明显低于野生型组,但无统计学意义。结论:POR*28基因多态性对硝苯地平在健康人体内药动学有显著的影响。OBJECtiVE To investigate the effect of POR ＊28 gene polymorphism on pharmacokinetics of nifedipine in Chi- nese healthy volunteers. METHODS PCR-sequencing was used to analyze the POR genotypes. Among forty-five volunteers there were fifteen POR ＊28 CC genotype, twenty-four CT genotype and six TT genotype. All volunteers were orally adminis- tered with nifedipine at a single dosage of 90 mg. Blood samples were collected at different time points and analyzed by a high performance liquid chromatography-mass spectrometry （HPLC-MS/MS） method. Pharmacokinetic parameters were calculated by 3P97 software. RESULTS There were significant differences in AUG0-∞, CL/F, and tl/2 among POR ＊28 CC, CT and TT genotype groups. The Cmax and tmax in subjects carrying TT genotype distinctly decreased compared with subjects with CC or CT genotype. CONCLUSION The POR ＊ 28 polymorphism affects the pharmacokinetics of nifedipine in Chinese healthy volun- teers.

关 键 词：硝苯地平 基因多态性 药动学 细胞色素P450氧化还原酶 

分 类 号：R969.1[医药卫生—药理学]