多药耐药基因多态性对泮托拉唑药动学的影响

发布时间：2018-01-22 00:34

  本文关键词： 泮托拉唑 P糖蛋白 多态性 单核苷酸 药动学　出处：《中国新药与临床杂志》2017年05期 　论文类型：期刊论文

【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(P0.05),C/C型和T/T型比较t_(max)、AUC_(0-max)差异显著(P0.05),C/T型和T/T型比较t_(max)差异显著(P0.05),其余药动学参数均无显著差异(P0.05)。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。
[Abstract]:Objective to investigate the effect of multidrug resistance (MDR1) C3435T gene polymorphism on pharmacokinetics of pam Tora in healthy volunteers. Methods Polymerase chain reaction (PCR) restriction fragment length polymorphism (PCR) was used to analyze the pharmacokinetics of Pam Tora. MDR1 genotyping was performed in 32 healthy subjects by PCR-RFLP. The plasma concentration of pam Tora was determined by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS) at different time points after a single fasting oral administration of Pam Tora Zol enteric-coated tablets (40 mg). The pharmacokinetic parameters were calculated and the differences of pharmacokinetic parameters among three genotypes were compared. Results MDR1C3435T C / C genotype. The distribution frequencies of C / T and T / T genotypes were 43.6% and 15.6%, respectively. The main pharmacokinetic parameters 蟻 max were 3.06 卤0.87). The tmax was 3.33 卤1.14 渭 g 路mL ~ (-1) and 3.52 卤1.07 渭 g 路mL ~ (-1), respectively. 2. 97 卤0. 75) and 2. 13 卤0. 65 hind tit / 2) were 2.38 卤2. 37) respectively. 1.46 卤0.26) and 2.87 卤3.25 hAUC (0-15) were 9.37 卤7.88). 6.33 卤2.20) and 11.01 卤11.32 渭 g 路h 路mL ~ (-1) AUC0- 鈭，

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