A comparison of the acid-inhibitory effects of esomeprazole and rabeprazole in relation to pharmacokinetics and CYP2C19 polymorphism

Aliment Pharmacol Ther. 2012 Apr;35(7):810-8. doi: 10.1111/j.1365-2036.2012.05014.x. Epub 2012 Feb 13.

Abstract

Background: Esomeprazole and rabeprazole are metabolised in the liver by means of the CYP2C19 enzyme, which has several functional genetic polymorphisms. Among Caucasians, 70% of the population has a fast metaboliser phenotype, 25-30% an intermediate and 2-5% a slow metaboliser phenotype. It is unknown whether different PPIs are affected to the same extent by these phenotypic differences.

Aim: To compare the acid-inhibitory effects of esomeprazole 40 mg and rabeprazole 20 mg in relation to CYP2C19 genotype and pharmacokinetics.

Methods: Eighteen healthy Helicobacter pylori-negative Caucasian subjects with CYP2C19*2-*6 and *17 genotype were included in a randomised investigator-blinded crossover study with esomeprazole 40 mg and rabeprazole 20 mg. Intragastric 24-h pH-monitoring was performed on days 0, 1 and 5 of oral dosing.

Results: Onset of acid inhibition during the first 4 h after administration did not differ significantly between PPIs. During the upright period, the proportion of time with pH >4 was significantly higher with esomeprazole compared to rabeprazole (52.2 vs. 40.3%, P = 0.003). At day 1 and 5, acid inhibition was significantly greater with esomeprazole than with rabeprazole (median intragastric pH: day 1: 3.7 vs. 3.0, P = 0.008; day 5: 4.7 vs. 3.8, P < 0.001; percentage of time pH >4: day 1: 45 vs. 39%, P = 0.054; day 5: 65 vs. 48%, P < 0.001). Differences in acid inhibition between wt/wt and wt/*2 genotype were significant for both PPIs.

Conclusions: Once-daily dosing with esomeprazole 40 mg provides a more effective and faster acid-inhibitory effect than rabeprazole 20 mg. The acid-inhibitory effect of esomeprazole and rabeprazole are both influenced by CYP2C19 polymorphism.

Publication types

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

MeSH terms

  • 2-Pyridinylmethylsulfinylbenzimidazoles / administration & dosage
  • 2-Pyridinylmethylsulfinylbenzimidazoles / pharmacokinetics*
  • Adolescent
  • Adult
  • Analysis of Variance
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Cross-Over Studies
  • Cytochrome P-450 CYP2C19
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Esomeprazole / administration & dosage
  • Esomeprazole / pharmacokinetics*
  • European Continental Ancestry Group / genetics*
  • Gastric Acid / metabolism*
  • Gastric Acidity Determination
  • Genotype
  • Humans
  • Hydrogen-Ion Concentration / drug effects
  • Liver / enzymology
  • Models, Theoretical
  • Polymorphism, Genetic*
  • Proton Pump Inhibitors / administration & dosage
  • Proton Pump Inhibitors / pharmacokinetics*
  • Rabeprazole
  • Young Adult

Substances

  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Proton Pump Inhibitors
  • Rabeprazole
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Esomeprazole