不同剂量泮托拉唑对CYP2C19 PMs消化性溃疡个体药动学和药效的影响

Research on the pharmacokinetics and pharmacodynamics of different doses of pantoprazole on CYP2C19 PMs in peptic ulcer patients

目的:研究不同剂量泮托拉唑治疗细胞色素氧化酶P450 2C19(CYP2C19)弱代谢型(poor metabolisers PMs)消化性溃疡(peptic ulcer PU)个体药动学和药效的影响。方法:聚合酶链限制性片断长度多态性(PCR-RFLP)分析确定CYP2C19PMs个体,高效液相色谱法测定药动学参数,电子胃镜复查观察疗效。结果:弱代谢型占受试者20%。CYP2C19PMs PU个体20mg组与40mg组主要药动学参数如下:AUC(5900.43±1046.92)和(5316.40±1437.00)μg.h.L-1;CL(3.67±1.79)和(8.09±1.93)mL.h-1;Cmax(1133.01±248.12)和(1242.08±160.71)μg.L-1;T1/2(2.74±0.48)和(2.82±0.81)/h,组间无显著性差异(P>0.05)。胃镜复查治疗效果20mg组与40mg组治愈率、愈合率、有效率分别为37.5%、37.5%、25%和50%、50%、25%,组间无显著性差异(P>0.05)。结论:CYP2C19PMs个体口服PAN20mg/d即可获得预期治疗效果;CYP2C19基因分型可为泮托拉唑治疗消化性溃疡的个体化方案提供依据。

ZHUO Yue, ZHANG Xue - mei （The First Affiliated Hospital of Jiamusi University, Jiarausi 154003, China） Objective： To investigate whether the pharmacodynamics and pharmacokinetics of different dos- es of pantoprazole are dependent on the cytochrome CYP2C19 poor metabolisers genotype status in peptic ulcer patients. Methods： The CYP2C19 poor metabolisers genotype status was determined by the PCR-RLFP, the serum concentrations of pantoprazole were measured by high performance liquid chromatography（HPLC）,and electronic gastroscope are used to observe its efficacy. Results： The frequency of the poor metabolizer of CYP 2C19 was 20 %. The AUC, CL, Cmax and T1/z,of pantoprazole in 20rag group and 40rag group were as fol- lows： AUC（5900. 43±1046.92）and（5316.40±1437.00）μg·h·L^-1 ;CL（3.67±1.79）and（8.09±1.93）mL· h^-1; Cmax（1133.01±4-248.12）and（1242.08±160. 71）μg·L-1;T1/2（2.74±0. 48）and（2. 82±0. 81）/h. The two groups did not show significant difference on statistics analysis （P 〉 0.05）. Cure rate, effective rate and healing rate of the two groups checked through electronic gastroscope were as follows： 37. 5%, 37. 5%, 25 % and 50 %, 50%, 25 %, and the two groups did not show significant difference on statistics analysis （P 〉 0.05）. Conclusions. A single oral dose of 40 mg pantoprazole one day can reach expected effect in CYP2C19 PMs pep- tic ulcer patientsr CYP2C19 gene analysis could provide evidence for individual project of pantoprazole treatment peptic ulcer.