CYP2D6基因多态性对帕罗西汀在中国健康人药动学影响  

Influence of CYP2D6 genetic polymorphism on pharmacokinetics of paroxetine in Chinese healthy people

作　　者：王蒙[1] 周文佳[1] 肖莉[1] 张全英[1] 

机构地区：[1]苏州大学附属第二医院药剂科,江苏苏州215004

出　　处：《中国新药与临床杂志》2012年第9期548-552,共5页Chinese Journal of New Drugs and Clinical Remedies

基　　金：苏州药学会-常州四药临床药学会科研基金(SYSD2010159)

摘　　要：目的研究中国健康人CYP2D6基因多态性对帕罗西汀药动学的影响。方法使用PCR-RFLP方法将23位志愿者分为3组:CYP2D6*1/*1组(n=5),CYP2D6*1/*10组(n=7),CYP2D6*10/*10组(n=11)。给予帕罗西汀20 mg单剂量口服,收集给药后96 h内的一系列血样,用LC-MS/MS法测定帕罗西汀的血药浓度并做药动学分析。结果与CYP2D6*1/*1组药动学参数相比,CYP2D6*1/*10组t_(max)、t1/2和CYP2D6*10/*10组t_(max)无显著差异(P>0.05);CYP2D6*1/*10、CYP2D6*10/*10组的ρ_(max)、AUC_(0-96 h)、AUC_(0-∞)、CL(F)、Vd和CYP2D6*10/*10组t_(1/2)均有显著差异(P<0.05或P<0.01)。结论 CYP2D6*10等位基因突变能引起代谢表型的改变,影响帕罗西汀在健康人的体内代谢。AIM To investigate the influence of CYP2D6 genetic polymorphism on pharmacokinetics of paroxetine in Chinese healthy people. METHODS Twenty-three Chinese volunteers genotyped for CYP2D6 were separated into three groups by PCR-RFLP： CYP2D6＊1/＊] group （n = 5）, CYP2D6＊1/＊10 group （n = 7）, and CYP2D6＊10/＊10 group （n = 11）. After administration of a single oral dose of paroxetine hydrochloride tablet 20 mg, blood samples were collected at various time points until 96 h. The plasma concentrations of paroxetine were measured by LC-MS/MS method and the pharmacokinetics disposition of them was analyzed. RESULTS Compared with CYP2D6＊1/＊1 group, the tmax and t1/2 in CYP2D6＊1/＊10 group and tmax in CYP2D6＊10/＊10 group had no significant differences （P 〉 0.05） ; ρmax, AUC0-96h, AUC0-∞, CL （F） and Vd of paroxetine in CYP2D6＊1/＊10 group and CYP2D6＊10/＊10 group, and t1/2 in CYP2D6＊10/＊10 group all had significant differences （P 〈 0.05 and P 〈 0.01）. CONCLUSION The allelic gene mutations of CYP2D6＊10 can cause the changes of metabolic phenotype and have effects on the metabolism of paroxetine in healthy human body.

关 键 词：细胞色素P450 CYP2D6 帕罗西汀 药动学 多态性 限制性片段长度 

分 类 号：R961[医药卫生—药理学]