A randomized open trial for comparison of proton pump inhibitors, omeprazole versus rabeprazole, in dual therapy for Helicobacter pylori infection in relation to CYP2C19 genetic polymorphism

Masatsugu Miyoshi, Motowo Mizuno, Kuniharu Ishiki, Yasuhiro Nagahara, Toshirou Maga, Tomomi Torigoe, Junichirou Nasu, Hiroyuki Okada, Kenji Yokota, Keiji Oguma, Takao Tsuji

Research output: Contribution to journalArticle

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Abstract

Background and Aim: The genetic polymorphism of cytochrome P450 (CYP) 2C19 has been shown to influence the efficacy of Helicobacter pylori eradication therapy with a proton pump inhibitor (PPI) and amoxicillin (so-called dual therapy). Omeprazole, a widely used PPI, and rabeprazole, a new PPI, are metabolized in different pathways in terms of CYP2C19 genetic polymorphisms. In this study, we compared the efficacy of omeprazole and rabeprazole in a 2-week dual therapy in relation to CYP2C19 polymorphism. Methods: One hundred and ninety-nine patients with peptic ulcer disease were randomly assigned to receive one of the following regimens: 500 mg t.i.d. amoxicillin together with either 20 mg b.i.d. omeprazole or 10 mg b.i.d rabeprazole. The eradication of H. pylori was evaluated by using a bacterial culture and a [13C]-urea breath test at 1-2 months after completion of treatment. Cytochrome P4502C19 polymorphism was analyzed by using polymerase chain reaction-restriction fragment length polymorphism. Results: Intention-to-treat-based cure rates for the omeprazole or rabeprazole regimens were 66.3% (95% CI, 56-75) and 62.4% (95% CI, 52-71), respectively, without significant difference. Cytochrome P4502C19 genetic polymorphism did not influence the cure rates in either of these regimens. We analyzed various factors associated with treatment failure (PPI, CYP2C19 genotype, and smoking habit) by using multiple logistic regression; smoking was the only significant independent factor for treatment failure. Conclusion: Omeprazole and rabeprazole were equally effective in combination with amoxicillin in eradicating H. pylori, irrespective of the PPI used (omeprazole or rabeprazole) and CYP2C19 genetic polymorphism. Smoking significantly decreased the cure rate of H. pylori infection in the dual therapy.

Original languageEnglish
Pages (from-to)723-728
Number of pages6
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume16
Issue number7
DOIs
Publication statusPublished - 2001

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Rabeprazole
Omeprazole
Proton Pump Inhibitors
Helicobacter Infections
Genetic Polymorphisms
Helicobacter pylori
Amoxicillin
Smoking
Cytochromes
Treatment Failure
Therapeutics
Breath Tests
Peptic Ulcer
Restriction Fragment Length Polymorphisms
Cytochrome P-450 Enzyme System
Habits
Urea
Cytochrome P-450 CYP2C19
Logistic Models
Genotype

Keywords

  • Cytochrome P450
  • Eradication therapy
  • Genetic polymorphism
  • Helicobacter pylori
  • Proton pump inhibitor
  • Smoking

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

A randomized open trial for comparison of proton pump inhibitors, omeprazole versus rabeprazole, in dual therapy for Helicobacter pylori infection in relation to CYP2C19 genetic polymorphism. / Miyoshi, Masatsugu; Mizuno, Motowo; Ishiki, Kuniharu; Nagahara, Yasuhiro; Maga, Toshirou; Torigoe, Tomomi; Nasu, Junichirou; Okada, Hiroyuki; Yokota, Kenji; Oguma, Keiji; Tsuji, Takao.

In: Journal of Gastroenterology and Hepatology (Australia), Vol. 16, No. 7, 2001, p. 723-728.

Research output: Contribution to journalArticle

Miyoshi, Masatsugu ; Mizuno, Motowo ; Ishiki, Kuniharu ; Nagahara, Yasuhiro ; Maga, Toshirou ; Torigoe, Tomomi ; Nasu, Junichirou ; Okada, Hiroyuki ; Yokota, Kenji ; Oguma, Keiji ; Tsuji, Takao. / A randomized open trial for comparison of proton pump inhibitors, omeprazole versus rabeprazole, in dual therapy for Helicobacter pylori infection in relation to CYP2C19 genetic polymorphism. In: Journal of Gastroenterology and Hepatology (Australia). 2001 ; Vol. 16, No. 7. pp. 723-728.
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abstract = "Background and Aim: The genetic polymorphism of cytochrome P450 (CYP) 2C19 has been shown to influence the efficacy of Helicobacter pylori eradication therapy with a proton pump inhibitor (PPI) and amoxicillin (so-called dual therapy). Omeprazole, a widely used PPI, and rabeprazole, a new PPI, are metabolized in different pathways in terms of CYP2C19 genetic polymorphisms. In this study, we compared the efficacy of omeprazole and rabeprazole in a 2-week dual therapy in relation to CYP2C19 polymorphism. Methods: One hundred and ninety-nine patients with peptic ulcer disease were randomly assigned to receive one of the following regimens: 500 mg t.i.d. amoxicillin together with either 20 mg b.i.d. omeprazole or 10 mg b.i.d rabeprazole. The eradication of H. pylori was evaluated by using a bacterial culture and a [13C]-urea breath test at 1-2 months after completion of treatment. Cytochrome P4502C19 polymorphism was analyzed by using polymerase chain reaction-restriction fragment length polymorphism. Results: Intention-to-treat-based cure rates for the omeprazole or rabeprazole regimens were 66.3{\%} (95{\%} CI, 56-75) and 62.4{\%} (95{\%} CI, 52-71), respectively, without significant difference. Cytochrome P4502C19 genetic polymorphism did not influence the cure rates in either of these regimens. We analyzed various factors associated with treatment failure (PPI, CYP2C19 genotype, and smoking habit) by using multiple logistic regression; smoking was the only significant independent factor for treatment failure. Conclusion: Omeprazole and rabeprazole were equally effective in combination with amoxicillin in eradicating H. pylori, irrespective of the PPI used (omeprazole or rabeprazole) and CYP2C19 genetic polymorphism. Smoking significantly decreased the cure rate of H. pylori infection in the dual therapy.",
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author = "Masatsugu Miyoshi and Motowo Mizuno and Kuniharu Ishiki and Yasuhiro Nagahara and Toshirou Maga and Tomomi Torigoe and Junichirou Nasu and Hiroyuki Okada and Kenji Yokota and Keiji Oguma and Takao Tsuji",
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T1 - A randomized open trial for comparison of proton pump inhibitors, omeprazole versus rabeprazole, in dual therapy for Helicobacter pylori infection in relation to CYP2C19 genetic polymorphism

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AU - Mizuno, Motowo

AU - Ishiki, Kuniharu

AU - Nagahara, Yasuhiro

AU - Maga, Toshirou

AU - Torigoe, Tomomi

AU - Nasu, Junichirou

AU - Okada, Hiroyuki

AU - Yokota, Kenji

AU - Oguma, Keiji

AU - Tsuji, Takao

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N2 - Background and Aim: The genetic polymorphism of cytochrome P450 (CYP) 2C19 has been shown to influence the efficacy of Helicobacter pylori eradication therapy with a proton pump inhibitor (PPI) and amoxicillin (so-called dual therapy). Omeprazole, a widely used PPI, and rabeprazole, a new PPI, are metabolized in different pathways in terms of CYP2C19 genetic polymorphisms. In this study, we compared the efficacy of omeprazole and rabeprazole in a 2-week dual therapy in relation to CYP2C19 polymorphism. Methods: One hundred and ninety-nine patients with peptic ulcer disease were randomly assigned to receive one of the following regimens: 500 mg t.i.d. amoxicillin together with either 20 mg b.i.d. omeprazole or 10 mg b.i.d rabeprazole. The eradication of H. pylori was evaluated by using a bacterial culture and a [13C]-urea breath test at 1-2 months after completion of treatment. Cytochrome P4502C19 polymorphism was analyzed by using polymerase chain reaction-restriction fragment length polymorphism. Results: Intention-to-treat-based cure rates for the omeprazole or rabeprazole regimens were 66.3% (95% CI, 56-75) and 62.4% (95% CI, 52-71), respectively, without significant difference. Cytochrome P4502C19 genetic polymorphism did not influence the cure rates in either of these regimens. We analyzed various factors associated with treatment failure (PPI, CYP2C19 genotype, and smoking habit) by using multiple logistic regression; smoking was the only significant independent factor for treatment failure. Conclusion: Omeprazole and rabeprazole were equally effective in combination with amoxicillin in eradicating H. pylori, irrespective of the PPI used (omeprazole or rabeprazole) and CYP2C19 genetic polymorphism. Smoking significantly decreased the cure rate of H. pylori infection in the dual therapy.

AB - Background and Aim: The genetic polymorphism of cytochrome P450 (CYP) 2C19 has been shown to influence the efficacy of Helicobacter pylori eradication therapy with a proton pump inhibitor (PPI) and amoxicillin (so-called dual therapy). Omeprazole, a widely used PPI, and rabeprazole, a new PPI, are metabolized in different pathways in terms of CYP2C19 genetic polymorphisms. In this study, we compared the efficacy of omeprazole and rabeprazole in a 2-week dual therapy in relation to CYP2C19 polymorphism. Methods: One hundred and ninety-nine patients with peptic ulcer disease were randomly assigned to receive one of the following regimens: 500 mg t.i.d. amoxicillin together with either 20 mg b.i.d. omeprazole or 10 mg b.i.d rabeprazole. The eradication of H. pylori was evaluated by using a bacterial culture and a [13C]-urea breath test at 1-2 months after completion of treatment. Cytochrome P4502C19 polymorphism was analyzed by using polymerase chain reaction-restriction fragment length polymorphism. Results: Intention-to-treat-based cure rates for the omeprazole or rabeprazole regimens were 66.3% (95% CI, 56-75) and 62.4% (95% CI, 52-71), respectively, without significant difference. Cytochrome P4502C19 genetic polymorphism did not influence the cure rates in either of these regimens. We analyzed various factors associated with treatment failure (PPI, CYP2C19 genotype, and smoking habit) by using multiple logistic regression; smoking was the only significant independent factor for treatment failure. Conclusion: Omeprazole and rabeprazole were equally effective in combination with amoxicillin in eradicating H. pylori, irrespective of the PPI used (omeprazole or rabeprazole) and CYP2C19 genetic polymorphism. Smoking significantly decreased the cure rate of H. pylori infection in the dual therapy.

KW - Cytochrome P450

KW - Eradication therapy

KW - Genetic polymorphism

KW - Helicobacter pylori

KW - Proton pump inhibitor

KW - Smoking

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