cyp2c19和il1基因多态性对ppis治疗消化性溃疡的影响及雷贝拉唑肝肠首过效应的初步分析word格式论文.docxVIP

时AUC及Cmax均随给药剂量增加而升高（P0.05），呈剂量依赖性；但T1/2、Tmax等参数各剂量间无明显差异(P0.05)；CL则随给药剂量增加而降低(P0.05)。肝脏提取率分别为84.8%、81.2%，肠道提取率分别为51.2%、56%。在抗生素对雷贝拉唑药代动力学影响的研究中，单用雷贝拉唑及雷贝拉唑与阿莫西林、雷贝拉唑与克拉霉素、雷贝拉唑与阿莫西林、克拉霉素合用时，各组间药代动力学参数AUC、T1/2z、Tmax，CLz/F经统计分析处理差异无显著性(P0.05)。结论（1）雷贝拉唑和埃索美拉唑能更加快速愈合溃疡，疗效优于奥美拉唑。（2）雷贝拉唑和埃索美拉唑为基础的三联疗法H.pylori根除率高，尤其在CYP2C19homEM基因型患者，雷贝拉唑和埃索美拉唑优于奥美拉唑。（3）奥美拉唑2周溃疡愈合率受CYP2C19基因多态性影响，存在个体差异；雷贝拉唑和埃索美拉唑2周溃疡愈合率和H.pylori根除率均不受CYP2C19基因多态性影响，个体差异小。（4）IL-1B-511基因多态性对PPIs三联疗法H.pylori根除率有影响。(5) 在大白兔体内经十二指肠、门静脉、外周静脉三种给药方式，雷贝拉唑药代动力学参数AUC、Cmax均呈剂量依赖性。(6) 雷贝拉唑在大白兔体内经历了较广泛的首过代谢，即肠道与肝脏对其首过效应。(7) 在大白兔体内,雷贝拉唑与阿莫西林、克拉霉素合用时，抗生素对雷贝拉唑药代动力学无影响。关键词消化性溃疡幽门螺杆菌细胞色素P450白介素－1基因多态性质子泵抑制剂药代动力学首过效应The Effects of CYP2C19 and IL-1 Genotypes on Proton Pump Inhibitors in Peptic Ulcer Diseases and the Study on Hepatic and Intestinal First-Pass Effects of RabeprazoleAbstractBackgroundandobjective:Protonpumpinhibitors(PPIs)arenowthemostimportantdrugsforacid-relateddiseases.PPIstogetherwithclarithromycinandamoxicillin/ormetronidazolehasbeenconsideredasthestandardfirst-lineregimenfor eradicationofHelicobecterpylori(H.pylori).Evenwiththecurrentlymosteffectivetreatmentregimens,onlyalittlemorethan80%ofpatientsshoweradicationofH. pylori.Thehostgeneticbackgroundshouldbeconsideredtodeterminetheoutcomeof PPI-basedtripletherapy.Geneticpolymorphismofinterleukin(IL)–1βandIL-1 receptorantagonist(IL-1rα)areassociatedwithdifferencesingastricacidsuppression andpolymorphismsofcytochromeP(CYP)2C19playvitalrolesinthemetabolismof PPIs. Thus,the polymorphismsmight affect H.pylori eradicationtherapy, asantibioticsusedintreatmentregimensmaybeacidsensitive.Wecomparedtheeffectsof esomeprazoleandrabeprazolevsomeprazoleontheulcerhealingandtheeradicationofH.pyloriinrelationtoCYP2C19,IL-1BandIL-1RNgenotypesinChinesepeople.Drugs that undergo extensive first-pass elimination often have low and variablebioavailability.The precise role of the hepatic and intestinal first pass effects on bioavailability of rabeprazole has not been clearly define