非静脉曲张性上消化道出血患者胃内酸性水平和CYP2C19基因多态性与奥美拉唑给药方式关系  

The relationship between gastric acid level,CYP2C19 gene polymorphism and omeprazole administration in patients with non-varicose upper gastrointestinal bleeding

作　　者：鄢家苗 许霞 YAN JIA-miao;XU Xia(Department of Pharmacy,Ankang Traditional Chinese Medicine Hospital,Ankang 725000,China)

机构地区：[1]安康市中医医院药剂科,陕西安康725000

出　　处：《中国中西医结合消化杂志》2020年第6期462-467,共6页Chinese Journal of Integrated Traditional and Western Medicine on Digestion

摘　　要：[目的]探究奥美拉唑(OME)在胃内酸性水平和细胞色素P450 2C19(CYP2C19)基因型和表型等因素影响下的最佳应用方法。[方法]对非静脉曲张性上消化道出血(NVUGIB)患者进行前瞻性研究。2015年3月~2018年12月收集分析了110例样本,其中包括48例OME静脉滴注给药和62例OME静脉注射给药患者。在内镜下止血术后,静脉滴注组给予80 mg OME静脉注射,之后OME静脉滴注组用8 mg/h OME连续静脉滴注72 h;静脉注射组在给予80 mg OME静脉注射后5 min内再每12 h接受40 mg OME静脉注射。在此过程中记录胃内酸性水平,分析CYP2C19变异等位基因(*2,*3,*17),测定血清中OME和5-羟奥美拉唑(5-OH-OME)的浓度。[结果]①OME给药方式与胃内pH值持续的不同时间段关系:2组胃内pH值>4和>6在0~12 h内均无明显区别。2组胃内pH值>4在0~48 h(滴注组vs.注射组,100.0%vs.96.8%,P=0.031)以及0~72 h(滴注组vs.注射组,100.0%vs.87.5%,P=0.001)差异有统计学意义。2组胃内pH值>6在0~72 h内(滴注组vs.注射组,97.4%vs.64.1%,P=0.036)差异有统计学意义。②OME给药方式与是否感染幽门螺杆菌(Hp)的关系:与未感染的患者相比,滴注组Hp感染患者的胃内pH值20 min(6.2 vs.4.8,P=0.16);40 min(6.5 vs.6.0,P=0.023);60 min(6.9 vs.6.3,P=0.009)更高。滴注组Hp感染患者的胃内pH值在给药后0 min^6 h增长(1.5vs.7.6,P=0.012)最大。但注射组在pH值>4和>6的平均时间百分比以及在不同给药时间上差异无统计学意义。③OME给药方式与CYP2C19基因型和表型的关系:在不同CYP2C19等位基因变异类型中,滴注组UM比EM更快使胃内pH值达到>6(P>0.05),而注射组EM似乎比UM更有效(P>0.05)。且给药方式与CYP2C19变异等位基因(*2,*3,*17)多态性无关。[结论]在NVUGIB患者中,无论CYP2C19基因多态性如何,OME单次注射治疗后,持续滴注给药比每12 h 1次注射给药在保持较高的胃内pH值中更有效。Hp感染可加速胃内pH的初始升高。[Objective] To explore the best application of omeprazole(OME)in intragastric pH,cytochrome P450 2 C19(CYP2 C19)genotype and phenotype.[Methods]A prospective study was performed on patients with non variceal upper gastrointestinal bleeding(NVUGIB).110 samples were collected and analyzed,including 48 intravenous OME bolus injection and 62 OME continuous intravenous infusion.After the achievement of endoscopic hemostasis,80 mg OME intravenous injection was given,followed by every 12 h or 8-mg/h continuous i.v.infusion.In the process,the gastric acid level was recorded,and the CYP2 C19 variant alleles(*2,*3,*17)were analyzed and the serum concentrations of OME and 5-hydroxyomeprazole(5-OH OME)were determined.[Results]①The relationship between the mode of OME administration and the duration of pH in the stomach:there was no significant difference between the two groups within 0~12 h when the pH in the stomach was>4 and>6.There were significant differences between the two groups when the pH value in stomach was more than 4 between 0~48 h(100% vs. 96.8%,P=0.031)and 0~72 h(100.0% vs. 87.5%,P=0.001).There was a significant difference between the two groups in 0~72 h(97.4% vs. 64.1%,P=0.036).②The relationship between the administration mode of OME and the infection of H.pylori:compared with the uninfected patients,the intragastric pH value of H.pylori infected patients in the infusion group was 20 min(6.2 to 4.8,P=0.16);40 min(6.5 to 6.0,P=0.023);60 min(6.9 to 6.3,P=0.009)higher.The intragastric pH value of H.pylori infected patients in the infusion group increased the most in 0-6 h after administration(1.5 vs. 7.6,P=0.012).However,there was no significant difference in the average time percentage of pH>4 and>6 and in the different administration time in the injection group.③The relationship between OME administration mode and CYP2 C19 genotype and phenotype:among the different CYP2 C19 allele variants,UM in the infusion group was faster than EM in achieving gastric pH value>6(P>0.05),while em in the injection group

关 键 词：非静脉曲张性上消化道出血 胃内PH值 奥美拉唑 细胞色素P4502C19 幽门螺杆菌 

分 类 号：R57[医药卫生—消化系统]