Inhibitory effect of troleandomycin on the metabolism of omeprazole is CYP2C19 genotype-dependent

Xenobiotica. 2003 Feb;33(2):211-21. doi: 10.1080/0049825021000023996.


1. Eighteen healthy CYP2C19 genotyped male subjects were administered a 20-mg oral dose of omeprazole (OP) alone or received troleandomycin (TAO) 500 mg daily for 2 days before the dose of OP was administered. Blood samples were obtained and OP 5-hydroxyomeprazole (5-OH-OP) and OP sulfone in plasma were determined by reversed-phase HPLC. 2. The mean C(max), AUC and CL for OP in poor metabolizers (PMs) were greater with TAO than without TAO. The C(max) and AUC of 5-OH-OP in PMs were significantly (p < 0.05) less with TAO than without TAO. The differences in 5-OH-OP between heterozygous extensive metabolizers (EMs) with TAO versus without TAO were similar to those observed in PMs, except for the AUC. However, in homozygous EMs, there were no statistical differences for the effect of TAO. 3. The effect of TAO on the metabolism of OP and its two principal metabolites differs in different genotype groups of CYP2C19. CYP3A4 not only plays a dominant role in the formation of OP sulfone, but also it contributes to the 5-hydroxylation of OP. Both CYP2C19 and CYP3A contribute to the further elimination of 5-OH-OP and OP sulfone.

Publication types

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

MeSH terms

  • Adult
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Ulcer Agents / pharmacokinetics*
  • Area Under Curve
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Aryl Hydrocarbon Hydroxylases / metabolism*
  • Cross-Over Studies
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism
  • DNA / biosynthesis
  • DNA / genetics
  • Genotype
  • Half-Life
  • Humans
  • Male
  • Mixed Function Oxygenases / genetics*
  • Mixed Function Oxygenases / metabolism*
  • Omeprazole / pharmacokinetics*
  • Polymorphism, Restriction Fragment Length
  • Reverse Transcriptase Polymerase Chain Reaction
  • Troleandomycin / pharmacology*


  • Anti-Bacterial Agents
  • Anti-Ulcer Agents
  • DNA
  • Cytochrome P-450 Enzyme System
  • Troleandomycin
  • Mixed Function Oxygenases
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • CYP3A protein, human
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human
  • Omeprazole