Effect of omeprazole on the pharmacokinetics of moclobemide according to the genetic polymorphism of CYP2C19

Clin Pharmacol Ther. 2001 Apr;69(4):266-73. doi: 10.1067/mcp.2001.114231.


Background: Moclobemide, an antidepressant with selective monoamine oxidase-A inhibitory action, is known to be metabolized by CYP2C19 and is also reported to be an inhibitor of CYP2C19, CYP2D6, and CYP1A2. To confirm the involvement of CYP2C19, we performed a pharmacokinetic interaction study.

Methods: The effect of omeprazole on the pharmacokinetics of moclobemide was studied in 16 healthy volunteers. The volunteer group comprised 8 extensive metabolizers and 8 poor metabolizers of CYP2C19, which was confirmed by genotyping. Subjects were randomly allocated into two sequence groups, and a single-blind, placebo-controlled, two-period crossover study was performed. In study I, a placebo was orally administered for 7 days. On the eighth morning, 300 mg of moclobemide and 40 mg of placebo were coadministered with 200 mL of water, and a pharmacokinetic study was performed. During study II, 40 mg of omeprazole was given each morning instead of placebo, and pharmacokinetic studies were performed on the first and eighth day with 300 mg of moclobemide coadministration.

Results: The inhibition of moclobemide metabolism was significant in extensive metabolizers even after a single dose of omeprazole. After daily administration of omeprazole for 1 week, the pharmacokinetic parameters of moclobemide and its metabolites in extensive metabolizers changed to values similar to those in poor metabolizers. In poor metabolizers, no remarkable changes in the pharmacokinetic parameters were observed.

Conclusion: Our results show that CYP2C19 is an important enzyme in the elimination of moclobemide and that it is extensively inhibited by omeprazole in extensive metabolizers, but not in poor metabolizers.

Publication types

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

MeSH terms

  • Adult
  • Antidepressive Agents / pharmacokinetics*
  • Area Under Curve
  • Aryl Hydrocarbon Hydroxylases*
  • Benzamides / pharmacokinetics
  • Cross-Over Studies
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 Enzyme Inhibitors
  • Cytochrome P-450 Enzyme System / genetics*
  • Cytochrome P-450 Enzyme System / physiology
  • Drug Interactions
  • Enzyme Inhibitors / pharmacology*
  • Genotype
  • Humans
  • Mixed Function Oxygenases / antagonists & inhibitors
  • Mixed Function Oxygenases / genetics*
  • Mixed Function Oxygenases / physiology
  • Moclobemide / pharmacokinetics*
  • Morpholines / pharmacokinetics
  • Omeprazole / pharmacology*
  • Polymorphism, Genetic*
  • Random Allocation


  • Antidepressive Agents
  • Benzamides
  • Cytochrome P-450 Enzyme Inhibitors
  • Enzyme Inhibitors
  • Morpholines
  • Ro 12-5637
  • Cytochrome P-450 Enzyme System
  • Ro 12-8095
  • Mixed Function Oxygenases
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Omeprazole
  • Moclobemide