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.
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.
Authors: Nicole G Hunfeld; Ron A Mathot; Daan J Touw; Ron H van Schaik; Paul G Mulder; Paul F Franck; Ernst J Kuipers; William P Geus Journal: Br J Clin Pharmacol Date: 2008-01-30 Impact factor: 4.335