奥美拉唑对胃内pH值和血浆胃泌素的影响取决于CYP2C19基因多态性。
Effects of omeprazole on intragastric pH and plasma gastrin are dependent on the CYP2C19 polymorphism.
作者信息
Sagar M, Tybring G, Dahl M L, Bertilsson L, Seensalu R
机构信息
Center of Gastroenterology, Departments of Surgery and Medicine, Clinical Research Center, Huddinge University Hospital, Stockholm, Sweden.
出版信息
Gastroenterology. 2000 Sep;119(3):670-6. doi: 10.1053/gast.2000.16515.
BACKGROUND & AIMS: Omeprazole is metabolized by cytochrome P450 (CYP2C19). The activity of this enzyme is polymorphic, with incidences of poor metabolizers (PMs), heterozygous extensive metabolizers (EMs), and homozygous EMs in white populations of 3%, 30%, and 67%, respectively. The importance of the CYP2C19 polymorphism for the effects of omeprazole on intragastric pH and plasma gastrin concentrations has been investigated.
METHODS
Twenty-five white patients were genotyped for CYP2C19 by allele-specific polymerase chain reaction amplification, and their Helicobacter pylori status was assessed by serology and with immunoblot analysis. Intragastric pH was monitored over 24 hours, and meal-stimulated plasma gastrin concentration was measured over 4 hours (AUC 4h) before (day 0) and during (day 8) treatment with 20 mg omeprazole once daily.
RESULTS
Eleven patients were homozygous for the wild-type allele (wt/wt), 12 were heterozygous EMs (wt/mut), and 2 were PMs (mut/mut). Median (95% confidence interval) 24-hour intragastric pH in the heterozygous EM group was 5.5 (range, 5.1-5. 9) compared with 3.1 (range, 2.7-3.6) in homozygous EMs (P < 0.0001) at day 8. The percentage of time with intragastric pH > 4 at day 8 was significantly higher in the wt/mut than wt/wt group (72.4% vs. 37.1%; P < 0.0001). H. pylori status had less influence than CYP2C19 on intragastric acidity. Omeprazole treatment increased meal-stimulated plasma gastrin concentrations from day 0 to day 8 in the homozygous EMs and heterozygous EMs by 16% (NS) and 157% (P = 0. 002), respectively. In heterozygous EMs, the gastrin increase was more pronounced in the H. pylori-positive group (226%) than H. pylori-negative group (80%; P = 0.02).
CONCLUSIONS
The effects of omeprazole on intragastric pH and plasma gastrin are dependent on the CYP2C19 polymorphism in patients with acid-related disorders.
背景与目的
奥美拉唑由细胞色素P450（CYP2C19）代谢。该酶的活性具有多态性，在白种人群中，慢代谢者（PMs）、杂合子快代谢者（EMs）和纯合子EMs的发生率分别为3%、30%和67%。已对CYP2C19基因多态性对奥美拉唑影响胃内pH值和血浆胃泌素浓度的重要性进行了研究。
方法
采用等位基因特异性聚合酶链反应扩增法对25例白种患者进行CYP2C19基因分型，通过血清学和免疫印迹分析评估其幽门螺杆菌感染状况。在每日一次服用20mg奥美拉唑治疗前（第0天）和治疗期间（第8天），监测24小时胃内pH值，并测量4小时（AUC 4h）进餐后刺激的血浆胃泌素浓度。
结果
11例患者为野生型等位基因纯合子（wt/wt），12例为杂合子EMs（wt/mut），2例为PMs（mut/mut）。在第8天，杂合子EM组的24小时胃内pH值中位数（95%置信区间）为5.5（范围5.1 - 5.9），而纯合子EMs组为3.1（范围2.7 - 3.6）（P < 0.0001）。在第8天，胃内pH值>4的时间百分比在wt/mut组显著高于wt/wt组（72.4%对37.1%；P < 0.0001）。幽门螺杆菌感染状况对胃内酸度的影响小于CYP2C19。奥美拉唑治疗使纯合子EMs组和杂合子EMs组进餐后刺激的血浆胃泌素浓度从第0天到第8天分别升高了16%（无统计学意义）和157%（P = 0.002）。在杂合子EMs中，幽门螺杆菌阳性组的胃泌素升高比幽门螺杆菌阴性组更明显（226%对80%；P = 0.02）。
结论
在患有酸相关疾病的患者中，奥美拉唑对胃内pH值和血浆胃泌素的影响取决于CYP2C19基因多态性。
Zotero 插件