Effects of clarithromycin on the metabolism of omeprazole in relation to CYP2C19 genotype status in humans

Clin Pharmacol Ther. 1999 Sep;66(3):265-74. doi: 10.1016/S0009-9236(99)70034-2.


Background and purpose: A triple therapy with omeprazole, amoxicillin (INN, amoxicilline), and clarithromycin is widely used for the eradication of Helicobacter pylori. Omeprazole and clarithromycin are metabolized by CYP2C19 and CYP3A4. This study aimed to elucidate whether clarithromycin affects the metabolism of omeprazole.

Methods: After administration of placebo or 400 mg clarithromycin twice a day for 3 days, 20 mg omeprazole and placebo or 400 mg clarithromycin were administered to 21 healthy volunteers. Plasma concentrations of omeprazole and clarithromycin and their metabolites were determined before and 1, 2, 3, 5, 7, 10, and 24 hours after dosing. CYP2C19 genotype status was determined by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

Results: Subjects were classified into three groups on the basis of PCR-RFLP analyses for CYP2C19: homozygous extensive metabolizer group (n = 6), heterozygous extensive metabolizer group (n = 11), and poor metabolizer group (n = 4). Mean area under the plasma concentration-time curves from 0 to 24 hours (AUC) of omeprazole in the homozygous extensive metabolizer, heterozygous extensive metabolizer, and poor metabolizer groups were significantly increased by clarithromycin from 383.9 to 813.1, from 1001.9 to 2110.4, and from 5589.7 to 13098.6 ng x h/mL, respectively. There were significant differences in the mean AUC values of clarithromycin among the three groups.

Conclusion: Clarithromycin inhibits the metabolism of omeprazole. Drug interaction between clarithromycin and omeprazole may underlie high eradication rates achieved by triple therapy with omeprazole, amoxicillin, and clarithromycin.

Publication types

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

MeSH terms

  • Adult
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Ulcer Agents / antagonists & inhibitors
  • Anti-Ulcer Agents / blood
  • Anti-Ulcer Agents / pharmacokinetics*
  • Area Under Curve
  • Aryl Hydrocarbon Hydroxylases*
  • Clarithromycin / pharmacology*
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 Enzyme System / genetics*
  • Enzyme Inhibitors / pharmacokinetics
  • Female
  • Genotype
  • Heterozygote
  • Homozygote
  • Humans
  • Male
  • Mixed Function Oxygenases / genetics*
  • Omeprazole / antagonists & inhibitors
  • Omeprazole / blood
  • Omeprazole / pharmacokinetics*
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Protein Synthesis Inhibitors / pharmacology*
  • Reference Values
  • Volunteers


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