The influence of CYP2C19 polymorphisms on exacerbating effect of rabeprazole in celecoxib-induced small bowel injury

Y. Nuki, Junji Umeno, E. Washio, Y. Maehata, Atsushi Hirano, M. Miyazaki, H. Kobayashi, Takanari Kitazono, T. Matsumoto, Motohiro Esaki

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: Simultaneous use of proton pump inhibitors (PPIs) has been shown to increase the risk of nonsteroidal anti-inflammatory drug (NSAID)-induced small bowel injury. Aim: To investigate whether polymorphisms of the cytochrome P450 2C19 gene (CYP2C19), encoding a key metabolising enzyme for PPIs, are associated with small bowel injury induced by celecoxib in combination with the PPI rabeprazole. Methods: Study participants included 55 healthy Japanese volunteers, who participated in the PPI-NSAID Kyushu University Study using video capsule endoscopy. For 2 weeks, 26 subjects were treated with celecoxib plus rabeprazole (rabeprazole group), and 29 subjects received celecoxib plus placebo (placebo group). All subjects were genotyped for CYP2C19 using real-time fluorescent polymerase chain reaction. Subjects were sub-classified as poor metabolizers or extensive metabolizers. The incidence and number of small bowel injuries were compared between poor metabolizers and extensive metabolizers in each group. Results: In the rabeprazole group, the incidence of small bowel injuries was significantly higher in poor metabolizers than in extensive metabolizers (85.7% vs 31.6%, P=.026). The number of mucosal injuries in the rabeprazole group was also significantly higher in poor metabolizers compared with extensive metabolizers (median [range] 3 [0-31] vs 0 [0-7], P=.01). In addition, we found a significant interaction between CYP2C19 genotype and concomitant use of rabeprazole in subjects at risk for celecoxib-induced small bowel injury. Conclusions: The CYP2C19 genotype might be associated with the risk of small bowel injury when celecoxib is combined with rabeprazole.

Original languageEnglish
Pages (from-to)331-336
Number of pages6
JournalAlimentary Pharmacology and Therapeutics
Volume46
Issue number3
DOIs
Publication statusPublished - Aug 1 2017

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Celecoxib
Rabeprazole
Cytochrome P-450 Enzyme System
Proton Pump Inhibitors
Wounds and Injuries
Genes
Anti-Inflammatory Agents
Genotype
Placebos
Capsule Endoscopy
Incidence
Pharmaceutical Preparations
Real-Time Polymerase Chain Reaction
Healthy Volunteers

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology
  • Pharmacology (medical)

Cite this

The influence of CYP2C19 polymorphisms on exacerbating effect of rabeprazole in celecoxib-induced small bowel injury. / Nuki, Y.; Umeno, Junji; Washio, E.; Maehata, Y.; Hirano, Atsushi; Miyazaki, M.; Kobayashi, H.; Kitazono, Takanari; Matsumoto, T.; Esaki, Motohiro.

In: Alimentary Pharmacology and Therapeutics, Vol. 46, No. 3, 01.08.2017, p. 331-336.

Research output: Contribution to journalArticle

Nuki, Y. ; Umeno, Junji ; Washio, E. ; Maehata, Y. ; Hirano, Atsushi ; Miyazaki, M. ; Kobayashi, H. ; Kitazono, Takanari ; Matsumoto, T. ; Esaki, Motohiro. / The influence of CYP2C19 polymorphisms on exacerbating effect of rabeprazole in celecoxib-induced small bowel injury. In: Alimentary Pharmacology and Therapeutics. 2017 ; Vol. 46, No. 3. pp. 331-336.
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AU - Nuki, Y.

AU - Umeno, Junji

AU - Washio, E.

AU - Maehata, Y.

AU - Hirano, Atsushi

AU - Miyazaki, M.

AU - Kobayashi, H.

AU - Kitazono, Takanari

AU - Matsumoto, T.

AU - Esaki, Motohiro

PY - 2017/8/1

Y1 - 2017/8/1

N2 - Background: Simultaneous use of proton pump inhibitors (PPIs) has been shown to increase the risk of nonsteroidal anti-inflammatory drug (NSAID)-induced small bowel injury. Aim: To investigate whether polymorphisms of the cytochrome P450 2C19 gene (CYP2C19), encoding a key metabolising enzyme for PPIs, are associated with small bowel injury induced by celecoxib in combination with the PPI rabeprazole. Methods: Study participants included 55 healthy Japanese volunteers, who participated in the PPI-NSAID Kyushu University Study using video capsule endoscopy. For 2 weeks, 26 subjects were treated with celecoxib plus rabeprazole (rabeprazole group), and 29 subjects received celecoxib plus placebo (placebo group). All subjects were genotyped for CYP2C19 using real-time fluorescent polymerase chain reaction. Subjects were sub-classified as poor metabolizers or extensive metabolizers. The incidence and number of small bowel injuries were compared between poor metabolizers and extensive metabolizers in each group. Results: In the rabeprazole group, the incidence of small bowel injuries was significantly higher in poor metabolizers than in extensive metabolizers (85.7% vs 31.6%, P=.026). The number of mucosal injuries in the rabeprazole group was also significantly higher in poor metabolizers compared with extensive metabolizers (median [range] 3 [0-31] vs 0 [0-7], P=.01). In addition, we found a significant interaction between CYP2C19 genotype and concomitant use of rabeprazole in subjects at risk for celecoxib-induced small bowel injury. Conclusions: The CYP2C19 genotype might be associated with the risk of small bowel injury when celecoxib is combined with rabeprazole.

AB - Background: Simultaneous use of proton pump inhibitors (PPIs) has been shown to increase the risk of nonsteroidal anti-inflammatory drug (NSAID)-induced small bowel injury. Aim: To investigate whether polymorphisms of the cytochrome P450 2C19 gene (CYP2C19), encoding a key metabolising enzyme for PPIs, are associated with small bowel injury induced by celecoxib in combination with the PPI rabeprazole. Methods: Study participants included 55 healthy Japanese volunteers, who participated in the PPI-NSAID Kyushu University Study using video capsule endoscopy. For 2 weeks, 26 subjects were treated with celecoxib plus rabeprazole (rabeprazole group), and 29 subjects received celecoxib plus placebo (placebo group). All subjects were genotyped for CYP2C19 using real-time fluorescent polymerase chain reaction. Subjects were sub-classified as poor metabolizers or extensive metabolizers. The incidence and number of small bowel injuries were compared between poor metabolizers and extensive metabolizers in each group. Results: In the rabeprazole group, the incidence of small bowel injuries was significantly higher in poor metabolizers than in extensive metabolizers (85.7% vs 31.6%, P=.026). The number of mucosal injuries in the rabeprazole group was also significantly higher in poor metabolizers compared with extensive metabolizers (median [range] 3 [0-31] vs 0 [0-7], P=.01). In addition, we found a significant interaction between CYP2C19 genotype and concomitant use of rabeprazole in subjects at risk for celecoxib-induced small bowel injury. Conclusions: The CYP2C19 genotype might be associated with the risk of small bowel injury when celecoxib is combined with rabeprazole.

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