不同细胞色素P450 2C19基因型肝病合并消化性溃疡患者泮托拉唑钠血药浓度测定  

Blood Drug Level of Pantoprazole Sodium in Liver Disease and Peptic Ulcer Patients with Different Genotypes of Cytochrome P450 2C19

作　　者：邵建国[1] 李克庆 蒋文[1] 郑露[1] 孙源源[1] 陆建荣[1] 

机构地区：[1]江苏省南通市第三人民医院消化内科,226006 [2]江苏省南通药品检验所

出　　处：《胃肠病学》2008年第5期297-299,共3页Chinese Journal of Gastroenterology

基　　金：江苏省南通市科技局社会发展科技计划立项课题(S5018)

摘　　要：背景:细胞色素P4502C19(CYP2C19)基因多态性对第一代质子泵抑制剂(PPI)的代谢有直接影响。CYP2C19的表达具有肝脏特异性。目的:观察不同CYP2C19基因型肝病合并消化性溃疡患者泮托拉唑钠代谢的差异,探讨肝脏病变对CYP2C19活性的影响。方法:合并消化性溃疡的21例原发性肝癌患者和22例脂肪肝患者纳入研究,25名健康志愿者作为对照。受试者口服泮托拉唑钠40mg/d一周,分别于服药1d和7d后采血,以反相高效液相色谱法测定血浆泮托拉唑钠浓度。结果:服药7d后,健康对照组、脂肪肝组和原发性肝癌组CYP2C19强代谢者的血浆泮托拉唑钠浓度均显著低于弱代谢者(P<0.05)。无论是强代谢者还是弱代谢者,服药7d后血浆泮托拉唑钠浓度均表现为原发性肝癌组>脂肪肝组>健康对照组(P<0.05)。结论:CYP2C19活性与肝病严重程度呈负相关。终末期肝病患者泮托拉唑钠血药浓度明显升高,尤其是CYP2C19弱代谢者。Background： Gene polymorphism of cytochrome P450 2C19 （CYP2C19） may influence the metabolism of first generation proton pump inhibitors （PPI）. The expression of CYP2C19 is liver-specific. Aims： To observe the metabolism of pantoprazole sodium in liver disease and peptic ulcer patients with different CYP2C19 genotypes, and to investigate the influence of liver disease on CYP2C19 activity. Methods： Twenty-one primary hepatocellular carcinoma （HCC） and 22 fatty liver patients complicated with peptic ulcer were enrolled, and 25 healthy volunteers served as controls. All subjects were given pantoprazole sodium 40 mg/d orally for 7 days. Blood samples were collected on the 1st and 7th day of medication. The plasma concentration of pantoprazole sodium was determined by reversed-phase high-performance liquid chromatography. Results： The plasma concentration of pantoprazole sodium on 7th day of medication in CYP2CI9 extensive metabolizers was significantly lower than that in poor metabolizers in all these three groups （P〈0.05）. Either in extensive metabolizers or in poor metabolizers, the plasma concentration of pantoprazole sodium in HCC group was higher than that in fatty liver group and in healthy controls on 7th day of medication （P〈0.05）. Conclusions： The activity of CYP2C19 is negatively correlated with severity of liver disease. The blood drug level of pantoprazole sodium increases in patients with end-stage liver disease, especially the CYP2C19 poor metabolizers.

关 键 词：细胞色素P-450 CYP2C19 基因型 泮托拉唑 肝疾病 消化性溃疡 

分 类 号：R575[医药卫生—消化系统] R573.1[医药卫生—内科学] R96[医药卫生—临床医学]