多药耐药基因多态性对泮托拉唑药动学的影响  

Effect of MDR1 gene polymorphism on pharmacokinetics of pantoprazole

作　　者：华雯妍[1] 俞蕴莉[1] 王蒙[1] 周文佳[1] 张全英[1] 

机构地区：[1]苏州大学附属第二医院临床药理实验室,江苏苏州215004

出　　处：《中国新药与临床杂志》2017年第5期295-299,共5页Chinese Journal of New Drugs and Clinical Remedies

基　　金：苏州市科技发展计划(应用基础研究-医药卫生)项目(SYSD2011138)

摘　　要：目的探讨健康志愿者的多药耐药基因(MDR1)C3435T基因多态性对泮托拉唑药动学的影响。方法用聚合酶链反应限制性片段长度多态性分析(PCR-RFLP)法对32例健康受试者进行MDR1基因分型,使用高效液相色谱-串联质谱法测定健康受试者单次空腹口服泮托拉唑肠溶片40 mg后不同时间点的泮托拉唑血浆浓度,计算药动学参数并比较3种不同基因型药动学参数间的差异。结果 MDR1C3435T C/C型、C/T型和T/T型基因型的分布频率分别为43.8%、40.6%和15.6%,主要的药动学参数ρmax分别为(3.06±0.87)、(2.80±0.83)和(3.52±1.07)μg·m L^(-1),tmax分别为(3.33±1.14)、(2.97±0.75)和(2.13±0.65)h,t_(1/2)分别为(2.38±2.37)、(1.46±0.26)和(2.87±3.25)h,AUC_(0-15)分别为(9.37±7.88)、(6.33±2.20)和(11.01±11.32)μg·h·m L^(-1),AUC0-∞分别为(11.24±12.42)、(6.36±2.21)和(14.21±18.35)μg·h·m L^(-1)。C/C型和C/T型比较各参数间无显著差异(P>0.05),C/C型和T/T型比较t_(max)、AUC_(0-max)差异显著(P<0.05),C/T型和T/T型比较t_(max)差异显著(P<0.05),其余药动学参数均无显著差异(P>0.05)。结论 MDR1基因多态性对泮托拉唑吸收速度和达峰前吸收程度有显著影响,但对总暴露量没有影响。AIM To investigate whether the multidrug resistance gene （MDR1） C3435T polymorphism would affect clarithromycin pharmacokinetics of pantoprazole in healthy volunteers. METHODS The genotype on MDRIC3435T in 32 healthy volunteers was detected by PCR-RFLP. The pantoprazole plasma concentrations of healthy volunteers after a single oral dose of pantoprazole enteric-coated tablet 40 mg were determined by HPLC- MS/MS, The pharmacokinetics of pantoprazole were calculated and compared among three genotypes. RESULTS The frequencies of MDRIC3435T C/C, C/T, TIT were 43.8%, 40.6% and 15.6%, pm were （3.06 ± 0.87）, （2.80 ± 0.83） and （3.52 ± 1.07） Ixg＇mL-1, tin=were （3.33 ± 1.14）, （2.97± 0.75） and （2.13 ± 0.65） h, tte were （2.38 ± 2.37）, （1.46 ± 0.26） and （2.87 ± 3.25） h, AUCo5 were （9.37 ± 7.88）, （6.33 ± 2.20） and （11.01 ±11.32） g-h-mL-1, AUC0 were （11.24 ±12.42）, （6.36 ± 2.21） and （14.21 ±18.35） μg·h·mL-1, respectively. There was no significant difference between C/C and C/T （P 〉 0.05）. t and AUC0 of pantoprazole had statistically significant differences between C/C and T/T （P 〈 0.05） , only t of pantoprazole had statistically significant difference between C/T and T/T （P 〈 0.05）. There were no significant differences in the parameters of pharmacokinetics among T/T and the other two genotypes （P 〉 0.05）. CONCLUSION The MDR1 gene polymorphism is an important factor influencing pantoprazole absorption rate and extent before tin. However there was no effect on the total amount of exposure.

关 键 词：泮托拉唑 P糖蛋白 多态性 单核苷酸 药动学 

分 类 号：R969[医药卫生—药理学]