CYP2D6基因多态性对帕罗西汀在中国健康人药动学影响

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。

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

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/*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 t_(max) and t_(1/2) in CYP2D6*1/*10 group and t_(max) in CYP2D6*10/*10 group had no significant differences(P>0.05);ρ_(max),AUC_(0-96h),AUC_(0-∞),CL(F) and V_d of paroxetine in CYP2D6*1/*10 group and CYP2D6*10/*10 group,and t_(1/2) 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.