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

Horng Yuan Lou, Chun Chao Chang, Ming Thau Sheu, Ying Chen Chen, Hsiu O. Ho

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32 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)55-64
Number of pages10
JournalEuropean Journal of Clinical Pharmacology
Volume65
Issue number1
DOIs
Publication statusPublished - Jan 2009

Fingerprint

Esomeprazole
Gastric Acid
Genotype
Pharmacokinetics
Cytochrome P-450 CYP2C19
Therapeutic Uses
Gastroesophageal Reflux
Stomach
Placebos
Clinical Trials

Keywords

  • CYP2C19
  • Esomeprazole
  • GERD
  • Intragastric pH
  • Polymorphism

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

Cite this

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title = "Optimal dose regimens of esomeprazole for gastric acid suppression with minimal influence of the CYP2C19 polymorphism",
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 = "CYP2C19, Esomeprazole, GERD, Intragastric pH, Polymorphism",
author = "Lou, {Horng Yuan} and Chang, {Chun Chao} and Sheu, {Ming Thau} and Chen, {Ying Chen} and Ho, {Hsiu O.}",
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T1 - Optimal dose regimens of esomeprazole for gastric acid suppression with minimal influence of the CYP2C19 polymorphism

AU - Lou, Horng Yuan

AU - Chang, Chun Chao

AU - Sheu, Ming Thau

AU - Chen, Ying Chen

AU - Ho, Hsiu O.

PY - 2009/1

Y1 - 2009/1

N2 - 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.

AB - 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.

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KW - Intragastric pH

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