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

Background & Aims: Omeprazole is metabolized by cytochrome P450 (CYP2C19). The activity of this enzyme is polymorphic, with incidences of poor metabol izers (PMs), heterozygous extensive metabolizers (EMs), and homozygous EMs in white populations of 3%, 30%, and 67%, respectively. The importance of t he CYP2C19 polymorphism for the effects of omeprazole on intragastric pH an d plasma gastrin concentrations has been investigated, Methods: Twenty-five white patients were genotyped for CYP2C19 by allele-specific polymerase ch ain reaction amplification, and their Helicobacter pylori status was assess ed by serology and with immunoblot analysis. Intragastric pH was monitored over 24 hours, and meal-stimulated plasma gastrin concentration was measure d 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 PM s (mut/mut), Median (95% confidence interval) 24-hour intragastric pH in th e 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 wi th 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 influ ence than CYP2C19 on intragastric acidity. Omeprazole treatment increased m eal-stimulated plasma gastrin concentrations from day 0 to day 8 in the hom ozygous EMs and heterozygous EMs by 16% (NS) and 157% (P = 0.002), respecti vely. In heterozygous EMs, the gastrin increase was more pronounced in the H. pylori-positive group (226%) than H. pylori-negative group (80%; P = 0.0 2). Conclusions: The effects of omeprazole on intragastric pH and plasma ga strin are dependent on the CYP2C19 polymorphism in patients with acid-relat ed disorders.