Effects of omeprazole on intragastric pH and plasma gastrin are dependent on the CYP2C19 polymorphism

奥美拉唑 CYP2C19型 内科学 胃泌素 幽门螺杆菌 化学 内分泌学 等位基因 餐食 医学 细胞色素P450 生物化学 新陈代谢 基因 分泌物
作者
Mohamed Sagar,Gunnel Tybring,M L Dahl,Leif Bertilsson,R Seensalu
出处
期刊:Gastroenterology [Elsevier BV]
卷期号:119 (3): 670-676 被引量:74
标识
DOI:10.1053/gast.2000.16515
摘要

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.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.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).The effects of omeprazole on intragastric pH and plasma gastrin are dependent on the CYP2C19 polymorphism in patients with acid-related disorders.
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