Evaluation of the relationship between polymorphisms in CYP2C19 and the pharmacokinetics of omeprazole, pantoprazole and rabeprazole

Pharmacogenomics. 2014;15(15):1893-901. doi: 10.2217/pgs.14.141.

Abstract

Aim: To evaluate the possible association between polymorphisms in CYP2C19 and the pharmacokinetics of omeprazole, rabeprazole and pantoprazole.

Materials & methods: 151 healthy volunteers were evaluated for polymorphisms in the CYP2C19 gene using real-time polymerase chain reaction. Plasma concentrations were measured using high-performance liquid chromatography coupled to mass spectrometry.

Results: Carriers of the *2 allele displayed poor metabolism for all the PPIs studied (around 50% decrease in clearance). Subjects with the *17 allele showed a light increase in clearance compared with *1/*1 (not significant).

Conclusion: CYP2C19*2 is associated with decreased clearance of all the PPIs, that could be associated with higher drug efficacy. CYP2C19*17 could increase clearance of these drugs, although the effect seems small.

Keywords: CYP2C19; pharmacogenetics; pharmacokinetics; proton-pump inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Pyridinylmethylsulfinylbenzimidazoles / administration & dosage
  • 2-Pyridinylmethylsulfinylbenzimidazoles / pharmacokinetics*
  • Adult
  • Cytochrome P-450 CYP2C19 / genetics*
  • Female
  • Genetic Association Studies
  • Genotype
  • Humans
  • Inactivation, Metabolic / genetics
  • Male
  • Omeprazole / administration & dosage
  • Omeprazole / pharmacokinetics*
  • Pantoprazole
  • Polymorphism, Genetic
  • Rabeprazole / administration & dosage
  • Rabeprazole / pharmacokinetics*

Substances

  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Rabeprazole
  • Pantoprazole
  • Cytochrome P-450 CYP2C19
  • Omeprazole