Pharmacogenetics

European Journal of Clinical Pharmacology

, Volume 65, Issue 1, pp 55-64

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

  • Horng-Yuan LouAffiliated withDivision of Gastroenterology, Department of Internal Medicine, Taipei Medical University and Hospital
  • , Chun-Chao ChangAffiliated withDivision of Gastroenterology, Department of Internal Medicine, Taipei Medical University and Hospital
  • , Ming-Thau SheuAffiliated withCollege of Pharmacy, Taipei Medical University
  • , Ying-Chen ChenAffiliated withCollege of Pharmacy, Taipei Medical University
  • , Hsiu-O HoAffiliated withCollege of Pharmacy, Taipei Medical University Email author 

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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

GERD Esomeprazole CYP2C19 Polymorphism Intragastric pH