Comparison of the kinetic disposition of and serum gastrin change by lansoprazole versus rabeprazole during an 8-day dosing scheme in relation to CYP2C19 polymorphism

Eur J Clin Pharmacol. 2001 Sep;57(6-7):485-92. doi: 10.1007/s002280100342.


Background: Little is known about differences in the disposition kinetics and pharmacological effects on gastrin levels between lansoprazole and rabeprazole given in a repeated dosing scheme with respect to the polymorphic CYP2C19.

Aim: To provide preliminary information that should be considered when prescribing proton-pump inhibitors (PPIs) for the treatment of acid-related diseases with reference to the CYP2C/9 genotypic status.

Methods: Helicobacter pylori-negative healthy volunteers were divided into the following three groups (n = 5 each) on the basis of genotyping for CYP2C19: homozygous (hmEMs) and heterozygous extensive metabolizers (htEMs), and poor metabolizers (PMs). All received once-daily 30-mg doses of lansoprazole or 10-mg doses of rabeprazole during an 8-day course in a crossover manner.

Results: The relative values for the area under the serum concentration-time curve (AUC) of lansoprazole and rabeprazole in the hmEMs, htEMs, and PMs after the final doses were 1:1.7:3.9 and 1:1.7:3.8, respectively. The relative AUCs of gastrin in the hmEMs, htEMs, and PMs were 1.6:2.6:3.1 for lansoprazole and 1.6:2.6:2.9 for rabeprazole, respectively.

Conclusion: The disposition kinetic behavior of the two PPIs is co-segregated with CYP2C19. The magnitude of CYP2C19-dependent drug availability in the systemic circulation and resulting gastrin response appears to be fairly similar between the two drugs within the same CYP2C19 genotypic groups after a multiple-dosing regimen.

Publication types

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

MeSH terms

  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Adenosine Triphosphatases / antagonists & inhibitors
  • Adult
  • Anti-Ulcer Agents / chemistry
  • Anti-Ulcer Agents / metabolism
  • Anti-Ulcer Agents / pharmacokinetics*
  • Area Under Curve
  • Aryl Hydrocarbon Hydroxylases*
  • Benzimidazoles / chemistry
  • Benzimidazoles / pharmacokinetics*
  • Cross-Over Studies
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism*
  • Female
  • Gastrins / blood*
  • Genotype
  • Humans
  • Lansoprazole
  • Male
  • Mixed Function Oxygenases / genetics
  • Mixed Function Oxygenases / metabolism*
  • Omeprazole / analogs & derivatives*
  • Omeprazole / chemistry
  • Omeprazole / metabolism
  • Omeprazole / pharmacokinetics*
  • Polymorphism, Genetic
  • Proton Pump Inhibitors
  • Proton-Translocating ATPases / antagonists & inhibitors
  • Rabeprazole


  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Anti-Ulcer Agents
  • Benzimidazoles
  • Gastrins
  • Proton Pump Inhibitors
  • Lansoprazole
  • Rabeprazole
  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Adenosine Triphosphatases
  • Proton-Translocating ATPases
  • Omeprazole