Randomized open trial for comparison of proton pump inhibitors in triple therapy for Helicobacter pylori infection in relation to CYP2C19 genotype

Tomoki Inaba, Motowo Mizuno, Kozou Kawai, Kenji Yokota, Keiji Oguma, Masatsugu Miyoshi, Susumu Take, Hiroyuki Okada, Takao Tsuji

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Background and aims: Genetic polymorphism of cytochrome P450 (CYP) 2C19 influences the efficacy of Helicobacter pylori eradication therapy with a proton pump inhibitor (PPI) and amoxicillin. However, in triple therapy (PPI plus amoxicillin and clarithromycin), little is known about the impact of CYP2C19 polymorphism, or the use of rabeprazole, which is not well metabolized by CYP2C19. The efficacy of three PPI (omeprazole, lansoprazole, and rabeprazole) in a 1-week triple regimen were compared in relation to CYP2C19 polymorphism. Method: One hundred and eighty-three patients were randomized to receive one of the following regimens: amoxicillin 500 mg t.i.d., clarithromycin 200 mg t.i.d., and PPI (omeprazole 20 mg, lansoprazole 30 mg, or rabeprazole 10 mg) b.i.d. CYP2C19 polymorphism was analyzed by PCR restriction fragment length polymorphism. Results: Intention-to-treat-based overall cure rates for omeprazole, lansoprazole or rabeprazole regimens were 83.1% (95% confidence interval (CI): 69-89%), 86.7% (CI: 75-93%), and 76.6% (CI: 64-85%), respectively, without significant difference. The cure rate of the rabeprazole regimen (but not the lansoprazole or omeprazole regimens) tended to be correlated with CYP2C19 genotypes (P = 0.076). In patients with a homozygous extensive metabolizer genotype, the per protocol-based cure rate with rabeprazole (62.5%) was significantly lower than that with lansoprazole (90.0%;P = 0.038). Conclusion: The overall cure rate of 1-week triple therapy for H. pylori eradication was not significantly different between regimens with omeprazole, lansoprazole or rabeprazole, but the impact of CYP2C19 genetic polymorphism on the cure rate appeared to differ between these PPI.

Original languageEnglish
Pages (from-to)748-753
Number of pages6
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume17
Issue number7
DOIs
Publication statusPublished - 2002

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Rabeprazole
Lansoprazole
Proton Pump Inhibitors
Helicobacter Infections
Helicobacter pylori
Omeprazole
Genotype
Amoxicillin
Clarithromycin
Genetic Polymorphisms
Confidence Intervals
Therapeutics
Cytochrome P-450 CYP2C19
Restriction Fragment Length Polymorphisms
Cytochrome P-450 Enzyme System
Polymerase Chain Reaction

Keywords

  • Helicobacter pylori
  • Proton pump inhibitor
  • Triple therapy

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

Randomized open trial for comparison of proton pump inhibitors in triple therapy for Helicobacter pylori infection in relation to CYP2C19 genotype. / Inaba, Tomoki; Mizuno, Motowo; Kawai, Kozou; Yokota, Kenji; Oguma, Keiji; Miyoshi, Masatsugu; Take, Susumu; Okada, Hiroyuki; Tsuji, Takao.

In: Journal of Gastroenterology and Hepatology (Australia), Vol. 17, No. 7, 2002, p. 748-753.

Research output: Contribution to journalArticle

Inaba, Tomoki ; Mizuno, Motowo ; Kawai, Kozou ; Yokota, Kenji ; Oguma, Keiji ; Miyoshi, Masatsugu ; Take, Susumu ; Okada, Hiroyuki ; Tsuji, Takao. / Randomized open trial for comparison of proton pump inhibitors in triple therapy for Helicobacter pylori infection in relation to CYP2C19 genotype. In: Journal of Gastroenterology and Hepatology (Australia). 2002 ; Vol. 17, No. 7. pp. 748-753.
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T1 - Randomized open trial for comparison of proton pump inhibitors in triple therapy for Helicobacter pylori infection in relation to CYP2C19 genotype

AU - Inaba, Tomoki

AU - Mizuno, Motowo

AU - Kawai, Kozou

AU - Yokota, Kenji

AU - Oguma, Keiji

AU - Miyoshi, Masatsugu

AU - Take, Susumu

AU - Okada, Hiroyuki

AU - Tsuji, Takao

PY - 2002

Y1 - 2002

N2 - Background and aims: Genetic polymorphism of cytochrome P450 (CYP) 2C19 influences the efficacy of Helicobacter pylori eradication therapy with a proton pump inhibitor (PPI) and amoxicillin. However, in triple therapy (PPI plus amoxicillin and clarithromycin), little is known about the impact of CYP2C19 polymorphism, or the use of rabeprazole, which is not well metabolized by CYP2C19. The efficacy of three PPI (omeprazole, lansoprazole, and rabeprazole) in a 1-week triple regimen were compared in relation to CYP2C19 polymorphism. Method: One hundred and eighty-three patients were randomized to receive one of the following regimens: amoxicillin 500 mg t.i.d., clarithromycin 200 mg t.i.d., and PPI (omeprazole 20 mg, lansoprazole 30 mg, or rabeprazole 10 mg) b.i.d. CYP2C19 polymorphism was analyzed by PCR restriction fragment length polymorphism. Results: Intention-to-treat-based overall cure rates for omeprazole, lansoprazole or rabeprazole regimens were 83.1% (95% confidence interval (CI): 69-89%), 86.7% (CI: 75-93%), and 76.6% (CI: 64-85%), respectively, without significant difference. The cure rate of the rabeprazole regimen (but not the lansoprazole or omeprazole regimens) tended to be correlated with CYP2C19 genotypes (P = 0.076). In patients with a homozygous extensive metabolizer genotype, the per protocol-based cure rate with rabeprazole (62.5%) was significantly lower than that with lansoprazole (90.0%;P = 0.038). Conclusion: The overall cure rate of 1-week triple therapy for H. pylori eradication was not significantly different between regimens with omeprazole, lansoprazole or rabeprazole, but the impact of CYP2C19 genetic polymorphism on the cure rate appeared to differ between these PPI.

AB - Background and aims: Genetic polymorphism of cytochrome P450 (CYP) 2C19 influences the efficacy of Helicobacter pylori eradication therapy with a proton pump inhibitor (PPI) and amoxicillin. However, in triple therapy (PPI plus amoxicillin and clarithromycin), little is known about the impact of CYP2C19 polymorphism, or the use of rabeprazole, which is not well metabolized by CYP2C19. The efficacy of three PPI (omeprazole, lansoprazole, and rabeprazole) in a 1-week triple regimen were compared in relation to CYP2C19 polymorphism. Method: One hundred and eighty-three patients were randomized to receive one of the following regimens: amoxicillin 500 mg t.i.d., clarithromycin 200 mg t.i.d., and PPI (omeprazole 20 mg, lansoprazole 30 mg, or rabeprazole 10 mg) b.i.d. CYP2C19 polymorphism was analyzed by PCR restriction fragment length polymorphism. Results: Intention-to-treat-based overall cure rates for omeprazole, lansoprazole or rabeprazole regimens were 83.1% (95% confidence interval (CI): 69-89%), 86.7% (CI: 75-93%), and 76.6% (CI: 64-85%), respectively, without significant difference. The cure rate of the rabeprazole regimen (but not the lansoprazole or omeprazole regimens) tended to be correlated with CYP2C19 genotypes (P = 0.076). In patients with a homozygous extensive metabolizer genotype, the per protocol-based cure rate with rabeprazole (62.5%) was significantly lower than that with lansoprazole (90.0%;P = 0.038). Conclusion: The overall cure rate of 1-week triple therapy for H. pylori eradication was not significantly different between regimens with omeprazole, lansoprazole or rabeprazole, but the impact of CYP2C19 genetic polymorphism on the cure rate appeared to differ between these PPI.

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