European Journal of Clinical Pharmacology

, 65:55

Optimal dose regimens of esomeprazole for gastric acid suppression with minimal influence of the CYP2C19 polymorphism

Authors

  • Horng-Yuan Lou
    • Division of Gastroenterology, Department of Internal MedicineTaipei Medical University and Hospital
  • Chun-Chao Chang
    • Division of Gastroenterology, Department of Internal MedicineTaipei Medical University and Hospital
  • Ming-Thau Sheu
    • College of PharmacyTaipei Medical University
  • Ying-Chen Chen
    • College of PharmacyTaipei Medical University
    • College of PharmacyTaipei Medical University
Pharmacogenetics

DOI: 10.1007/s00228-008-0552-0

Cite this article as:
Lou, H., Chang, C., Sheu, M. et al. Eur J Clin Pharmacol (2009) 65: 55. doi:10.1007/s00228-008-0552-0

Abstract

Objective

In this pilot study, we attempted to determine the optimal dosage regimens of esomeprazole for treatment of GERD with minimal influence of the CYP2C19 polymorphism through a study of the pharmacokinetics and pharmacodynamics of esomeprazole given at 3 different dosage regimens with the same total daily dose.

Methods

Each of the 3genotypes of CYP2C19, homozygous extensive metabolizers (homEMs), heterozygous EMS (hetEMs), and poor metabolizers (PMs) were recruited in this clinical trial. Subjects were given a placebo followed by the administration of esomeprazole, at a dose of 40 mg once daily (40QD), 20 mg twice daily (20TD), or 10 mg 4 times daily (10Q4D) for 7 days. Twenty-four-hour and nocturnal intragastric pH and plasma esomeprazole concentrations were all determined on day 7.

Results

The pharmacokinetic parameters and dynamic characteristics differed among the 3 CYP2C19 genotype groups. With esomeprazole 40QD, gastric acid suppression was insufficient to achieve a therapeutic effect, while 20TD and 10Q4D were found to be effective in controlling both daytime and nocturnal gastric acidity for all 3 genotype groups.

Conclusions

It was confirmed that intragastric pH values and plasma esomeprazole concentrations potentially depended on the CYP2C19 genotype status for treatment with esomeprazole. Dosage regimens of divided doses of 20TD or 10Q4D esomeprazole yielded improved antisecretory effects with a minimal influence of CYP2C19 polymorphisms.

Keywords

GERDEsomeprazoleCYP2C19PolymorphismIntragastric pH

Copyright information

© Springer-Verlag 2008