CYP2C19 genotype-related efficacy of omeprazole for the treatment of infection caused by Helicobacter pylori

Clin Pharmacol Ther. 1999 Nov;66(5):528-34. doi: 10.1016/S0009-9236(99)70017-2.

Abstract

Objectives: Omeprazole is used for the treatment of infection caused by Helicobacter pylori, and it is metabolized by the polymorphic cytochrome P4502C19 (CYP2C19). We have found that the anti-H pylori efficacy by the combination of omeprazole and antibiotics is related to the CYP2C19 genotype.

Methods: One hundred eight patients with cultured H pylori-positive gastritis or peptic ulcer were treated with three regimens: quadruple treatment without proton pump inhibitors (n = 25), dual treatment with omeprazole and amoxicillin (INN, amoxicilline) (n = 26), and triple treatment with omeprazole, amoxicillin, and clarithromycin (n = 57). The CYP2C19 genotype was determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and the assessment of the eradication of H pylori was based on all negative examinations, including culture, histology, and 13C-urea breath test.

Results: The eradication rates for the extensive metabolizers were 50% and 86% for the dual and triple treatments, respectively. In contrast, all of the poor metabolizers treated with omeprazole and antibiotics (n = 15) showed an eradication of H pylori.

Conclusion: The anti-H pylori effect of dual treatment is highly efficient for CYP2C19 poor metabolizers, which suggests that clarithromycin is not necessary as a first line of therapy for this type of patients. Genotyping can provide a choice for the optimal regimen based on individual CYP2C19 genotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amoxicillin / therapeutic use
  • Antacids / therapeutic use
  • Anti-Bacterial Agents / therapeutic use
  • Anti-Ulcer Agents / pharmacology*
  • Aryl Hydrocarbon Hydroxylases*
  • Bismuth / therapeutic use
  • Clarithromycin / therapeutic use
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 Enzyme Inhibitors*
  • Cytochrome P-450 Enzyme System / genetics*
  • Drug Therapy, Combination
  • Enzyme Inhibitors / pharmacology*
  • Gastritis / drug therapy*
  • Gastritis / microbiology
  • Genotype
  • Helicobacter Infections / drug therapy*
  • Helicobacter Infections / microbiology
  • Helicobacter pylori / drug effects*
  • Histamine H2 Antagonists / therapeutic use
  • Humans
  • Metronidazole / therapeutic use
  • Mixed Function Oxygenases / antagonists & inhibitors*
  • Mixed Function Oxygenases / genetics*
  • Omeprazole / pharmacology*
  • Penicillins / therapeutic use
  • Peptic Ulcer / drug therapy*
  • Peptic Ulcer / microbiology
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Protein Synthesis Inhibitors / therapeutic use
  • Treatment Outcome

Substances

  • Antacids
  • Anti-Bacterial Agents
  • Anti-Ulcer Agents
  • Cytochrome P-450 Enzyme Inhibitors
  • Enzyme Inhibitors
  • Histamine H2 Antagonists
  • Penicillins
  • Protein Synthesis Inhibitors
  • Metronidazole
  • Amoxicillin
  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Clarithromycin
  • bismuth subnitrate
  • Omeprazole
  • Bismuth