CYP2C19 genotype status and intragastric pH during dosing with lansoprazole or rabeprazole

Abstract

Background: CYP2C19 has an important role in the catabolism of several proton pump inhibitors. However, the relative contribution of CYP2C19-mediated metabolism varies among the different proton pump inhibitors. Aim: To determine the effect of CYP2C19 genotype status on intragastric pH during dosing with lansoprazole or rabeprazole. Subjects and methods: The subjects were 20 male volunteers without Helicobacter pylori infection. Their CYP2C19 genotype status was determined by a polymerase chain reaction-restriction fragment length polymorphism method. Twenty-four-hour monitoring of intragastric acidity was performed three times: once without medication, once on the last day of a 7-day course of rabeprazole, and once on the last day of a 7-day course of lansoprazole. Results: Subjects were divided into three groups on the basis of their CYP2C19 genotype status: homozygous extensive metabolizers (homo-EMs, n = 7), heterozygous extensive metabolizers (hetero-EMs, n = 9), and poor metabolizers (PMs, n = 4). The median pH during rabeprazole administration was not influenced by CYP2C19 genotype. On the other hand, the median pH in PMs during lansoprazole dosing was higher than in homo-EMs and hetero-EMs. The percentage of time with pH < 4.0 had a similar tendency to that of median pH. Conclusion: CYP2C19 genotype status influences gastric acid suppression by lansoprazole, but not by rabeprazole.