CYP2C19 genotype status and effect of omeprazole on intragastric pH in humans

Clin Pharmacol Ther. 1999 May;65(5):552-61. doi: 10.1016/S0009-9236(99)70075-5.

Abstract

Objective: Omeprazole is metabolized by genetically determined S-mephenytoin 4'-hydroxylase (CYP2C19) in the liver. This study aimed to determine whether the effect of omeprazole on intragastric pH depends on CYP2C19 genotype status.

Methods: CYP2C19 genotype status for 2 mutations associated with the poor metabolizer phenotype was determined by a polymerase chain reaction-restriction fragment length polymorphism method in 16 healthy volunteers. Helicobacterpylori status was determined by serology and the [13C]urea breath test. After a single oral administration of 20 mg omeprazole or a placebo, intragastric pH values were recorded for 24 hours. Plasma levels of omeprazole and its 2 metabolites and gastrin were measured before and 1, 2, 3, 5, 7, 10, and 24 hours after administration.

Results: Fifteen of the 16 subjects were H pylori negative. Five of the 15 subjects were homozygous extensive metabolizers, 4 were heterozygous extensive metabolizers, and 6 were poor metabolizers. After omeprazole administration, significant differences in mean intragastric pH values and plasma levels of gastrin, omeprazole and its metabolites were observed among the 3 groups, whereas no significant differences in these parameters were observed with the placebo administration.

Conclusions: The effect of omeprazole on intragastric pH significantly depends on CYP2C19 genotype status. The genotyping test of CYP2C19 may be useful for an optimal prescription of omeprazole.

Publication types

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

MeSH terms

  • Adult
  • Anti-Ulcer Agents / pharmacology*
  • Area Under Curve
  • Aryl Hydrocarbon Hydroxylases*
  • Asian Continental Ancestry Group / genetics
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 Enzyme Inhibitors*
  • Cytochrome P-450 Enzyme System / genetics*
  • Enzyme Inhibitors / pharmacology*
  • Female
  • Gastric Mucosa / metabolism*
  • Gastrins / blood*
  • Genotype
  • Helicobacter Infections / metabolism
  • Helicobacter Infections / microbiology
  • Helicobacter pylori / isolation & purification
  • Humans
  • Hydrogen-Ion Concentration
  • Japan
  • Male
  • Mixed Function Oxygenases / antagonists & inhibitors*
  • Mixed Function Oxygenases / genetics*
  • Omeprazole / pharmacology*
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Reference Values
  • Stomach / microbiology

Substances

  • Anti-Ulcer Agents
  • Cytochrome P-450 Enzyme Inhibitors
  • Enzyme Inhibitors
  • Gastrins
  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Omeprazole