[1]周霖,薛文华,张海朋,等.CYP2D6基因多态性对帕罗西汀在河南汉族健康受试者体内药代动力学的影响[J].郑州大学学报(医学版),2014,(06):841.
 ZHOU Lin,XUE Wenhua,ZHANG Haipeng,et al.Influence of CYP2D6 genetic polymorphism on pharmacokinetics of paroxetine in Henan Han healthy subjects[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2014,(06):841.
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CYP2D6基因多态性对帕罗西汀在河南汉族健康受试者体内药代动力学的影响
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《郑州大学学报(医学版)》[ISSN:1671-6825/CN:41-1340/R]

卷:
期数:
2014年06期
页码:
841
栏目:
应用研究
出版日期:
2014-11-20

文章信息/Info

Title:
Influence of CYP2D6 genetic polymorphism on pharmacokinetics of paroxetine in Henan Han healthy subjects
作者:
周霖薛文华张海朋刘克锋赵杰#
郑州大学第一附属医院药学部 郑州 450052
Author(s):
ZHOU LinXUE WenhuaZHANG HaipengLIU KefengZHAO Jie
Department of Pharmacy, the First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052
关键词:
CYP2D6帕罗西汀基因多态性药代动力学河南汉族
Keywords:
CYP2D6paroxetinegenetic polymorphismpharmacokineticsHenanHan population
分类号:
R969.1
摘要:
目的:研究CYP2D6基因多态性对帕罗西汀在河南汉族健康受试者体内药代动力学的影响。方法:河南汉族健康受试者48人,使用PCRRFLP技术对其进行CYP2D6基因型检测。受试者单剂量(7.5 mg)口服甲磺酸帕罗西汀胶囊后,收集120 h内的系列血样,用建立的LCMS/MS法测定血浆帕罗西汀浓度,绘制药时曲线,进行药代动力学分析。结果:男性CYP2D6*1/*1型受试者9人,CYP2D6*1/*10型21人;女性CYP2D6*1/*1型受试者5人,CYP2D6*1/*10型13人;未检测到CYP2D6*10/*10型;男、女CYP2D6基因型分布差异无统计学意义(χ2=0.027,P>0.999)。与CYP2D6*1/*1型男性受试者比较,CYP2D6*1/*10型男性受试者tmax、t1/2无明显变化(Z=1.145,t=1.400,P>0.05),CL(F)、Vd降低(Z=2.557,t=2.104,P<0.05),ρmax、AUC0120和AUC0∞增加(Z=2.421、2.512、2.557,P<0.05)。与CYP2D6*1/*1型女性受试者比较,CYP2D6*1/*10型女性受试者ρmax、tmax、t1/2及Vd无明显变化(Z=1.992、1.921,t=2.117、1.905,P>0.05),但 CL(F)降低(Z=2.021,P<0.05), AUC0120和AUC0∞增加(Z=2.021、2.021,P<0.05)。结论:CYP2D6*10突变等位基因可影响甲磺酸帕罗西汀在河南汉族健康人群体内的代谢。
Abstract:
Aim: To investigate the influence of CYP2D6 genetic polymorphism on pharmacokinetics of paroxetine in Henan Han healthy people.Methods: A total of 48 Han healthy volunteers from Henan Province were subjected to detect genetic polymorphied by PCRRFLP method. The volunteers were given a single oral dose of paroxetine mesylate capsule(7.5 mg), and blood samples were collected at different time points until 120 h. The concentrations of paroxetine in plasma were measured by LCMS/MS method, and the pharmacokinetics was analyzed.Results: There were 9 males with CYP2D6*1/*1, 21 with CYP2D6*1/*10,5 females with CYP2D6*1/*1 and 13 with CYP2D6*1/*10, and the distribution of CYP2D6 genetic polymorphism between the male and the female had no difference(χ2=0.027,P>0.999). Compared with the male with CYP2D6*1/*1, tmax,t1/2 of the male CYP2D6*1/*10 subjects had no changes(Z=1.145,t=1.400,P>0.05), CL(F) and Vd decreased(Z=2.557,t=2.104,P<0.05), ρmax,AUC0120 and AUC0∞ increased(Z=2.421,2.512,2.557,P<0.05). Compared with the female CYP2D6*1/*1 subjects, ρmax,tmax,t1/2 and Vd of the females with CYP2D6*1/*10 had no changes(Z=1.992,1.921,t=2.117,1.905,P>0.05), CL(F) decreased(Z=2.021,P<0.05), AUC0120 and AUC0∞ increased(Z=2.021,2.021,P<0.05).Conclusion: The mutation CYP2D6*10 could lead to the metabolic phenotype changes of paroxetine mesylate in Henan Han healthy subjects.

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备注/Memo

备注/Memo:
#通讯作者,男,1969年5月生,博士,教授,主任药师,研究方向:临床药学、药物基因组学与药代动力学,Email:zhaojie@zzu.edu.cn
更新日期/Last Update: 2014-11-26