CYP2C19基因多态性对含泮托拉唑四联法治疗幽门螺杆菌疗效的影响Impact of CYP2C19 polymorphism on eradication of Helicobacter pylori using pantoprazole-based quadruple therapy
黄译莹;李玲玲;孙环环;卫金歧;
摘要(Abstract):
目的探讨CYP2C19基因多态性对含泮托拉唑的四联疗法治疗幽门螺杆菌(Hp)疗效的影响,并观察CYP2C19基因多态性与质子泵抑制剂药物不良反应的相关性。方法 113例经电子胃镜或14C呼气试验证实Hp阳性同时有反复的消化道症状的慢性胃炎患者,给予泮托拉唑40 mg,bid+枸橼酸铋钾220 mg,bid+左氧氟沙星片0. 5 g,qd+阿莫西林克拉维酸钾0. 914 g,bid四联疗法根除Hp,疗程10 d,疗程结束后4~6周内行14C呼气试验评估疗效。采用多聚酶链-限制性片段长度多态性方法检测CYP2C19基因多态性,并据其分组,即强代谢表型(EM)组、中间代谢表型(IM)组和弱代谢表型(PM)组。观察各组间Hp根除率、临床症状缓解情况和不良反应发生情况。结果 (1)10 d含泮托拉唑四联方案Hp总根除率为78. 8%,CYP2C19 EM型、IM型和PM型的Hp根除率分别为72. 1%、80. 0%、89. 5%,各基因型间Hp根除率差异无统计学意义(P>0. 05);(2)该四联疗法总症状缓解率为93. 8%;出现不良反应8人,总的不良反应发生率7. 07%,EM、IM和PM组不良反应发生率分别为4. 65%、1. 96%、26. 3%,组间差异有统计学意义(P <0. 01)。结论 CYP2C19基因多态性对含泮托拉唑的四联法根除Hp的疗效影响不大。有必要进行大样本的研究,并考虑更多的因素对其疗效的影响。
关键词(KeyWords): CYP2C19;基因多态性;幽门螺杆菌;根除率;泮托拉唑
基金项目(Foundation):
作者(Authors): 黄译莹;李玲玲;孙环环;卫金歧;
DOI: 10.19577/j.1007-4406.2018.05.008
参考文献(References):
- [1]全国幽门螺杆中华医学会消化病学分会幽门螺杆菌学组等,第四次全国幽门螺杆菌感染处理共识报告[D].中华内科杂志,2012,51(10):823.
- [2]PADOL S,YUAN Y,THABANE M,et al. The effect of CYP2C19polymorphisms on H. pylori eradication rate in dual and triple firstline PPI therapies:a meta-analysis[J]. Am J Gastroenterol,2006,101(7):1467.
- [3]崔梅花,胡伏莲,姜红玉,等.泮托拉唑三联与奥美拉唑三联疗法根除幽门螺杆菌的对比研究[J].中华医学杂志,2002,82(18):1245
- [4]周健,吕虹,康熙雄.中国汉族人群不同性别、年龄、体重指数之间细胞色素氧化酶CYP2C19基因多态性的检测[J].中国临床药理学与治疗学,2007,12(2):208.
- [5]KARACA R O,KALKISIM S,ALTINBAS A,et al. Effects of genetic polymorphisms of cytochrome P450 enzymes and MDR1 transporter on pantoprazole metabolism and Helicobacter pylori eradication[J].Basic Clin Pharmacol Toxicol,2017,2(120):199.
- [6]SIMON N,FINZI J,CAYLA G,et al. Omeprazole,pantoprazole,and CYP2C19 effects on clopidogrel pharmacokinetic-pharmacodynamic relationships in stable coronary artery disease patients[J]. Eur J Clin Pharmacol,2015,71(9):1059.
- [7]SAHARA S,SUGIMOTO M,UOTANI T,et al. Twice-daily dosing of esomeprazole effectively inhibits acid secretion in CYP2C19 rapid metabolisers compared with twice-daily omeprazole,rabeprazole or lansoprazole[J]. Aliment Pharmacol Ther,2013,38(9):1129.
- [8] FURUTA T,SHIRAI N,SUGIMOTO M,et al. Influence of CYP2C19 pharmacogenetic polymorphism on proton pump inhibitor-based therapies[J]. Drug Metab Pharmacokinet,2005,20(3):157.
- [9]LEE J Y,KIM N,KIM M S,et al. Factors affecting first-line triple therapy of Helicobacter pylori including CYP2C19 genotype and antibiotic resistance[J]. Digestive Diseases and Sciences,2011,6(59):1235.
- [10]唐惠林,张婷,翟所迪,等. CYP2C19基因多态性对质子泵抑制剂补救疗法根除幽门螺旋杆菌疗效影响的荟萃分析[J].中国医院药学杂志,2013,33(18):1520.
- [11]GRAHAM D Y,LU H,YAMAOKA Y,et al. A report card to grade Helicobacter pylori therapy[J]. Helicobacter,2007,12(4):258.
- [12]卫金歧,黄雪平,农高惠.广东珠海地区慢性胃炎患者幽门螺杆菌的体外多重耐药性研究[J].山东医药,2013,42(53):234.
- [13]曾毅,叶雨彤,梁德森.阿莫西林与阿莫西林克拉维酸钾治疗幽门螺旋杆菌感染疗效的Meta分析[N].宁夏医科大学学报,2015,37(4):429.
- [14]李睿,庞伟. 2种根除幽门螺杆菌方案的比较研究[J].中国中西医结合消化杂志,2007,15(6):398.