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

Aliment Pharmacol Ther. 2000 Oct;14(10):1259-66. doi: 10.1046/j.1365-2036.2000.00840.x.

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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Adult
  • Anti-Ulcer Agents / pharmacology*
  • Aryl Hydrocarbon Hydroxylases*
  • Benzimidazoles / pharmacology*
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 Enzyme System / genetics*
  • Enzyme Inhibitors / pharmacology*
  • Gastric Acid / metabolism
  • Gastric Acid / physiology*
  • Gastric Acidity Determination
  • Genotype
  • Humans
  • Hydrogen-Ion Concentration
  • Lansoprazole
  • Male
  • Middle Aged
  • Mixed Function Oxygenases / genetics*
  • Omeprazole / analogs & derivatives*
  • Omeprazole / pharmacology
  • Polymorphism, Restriction Fragment Length
  • Proton Pump Inhibitors*
  • Rabeprazole

Substances

  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Anti-Ulcer Agents
  • Benzimidazoles
  • Enzyme Inhibitors
  • Proton Pump Inhibitors
  • Lansoprazole
  • Rabeprazole
  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Omeprazole