CYP2C19 genotype related effect of omeprazole on intragastric pH and antimicrobial stability

Tomoko Kita, Yusuke Tanigawara, Nobuo Aoyama, Takashi Hohda, Yoshie Saijoh, Fusao Komada, Toshiyuki Sakaeda, Katsuhiko Okumura, Toshiyuki Sakai, Masato Kasuga

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Purpose. A combination of proton pump inhibitors and antimicrobials has been applied as an anti-Helicobacter pylori (H. pylori) therapy. Omeprazole, one of the proton pump inhibitors, is metabolized by CYP2C19, which exhibits genetic polymorphism. It was reported previously that the overall anti-H, pylori efficacy can be related to the CYP2C19 genotype. The main aim of the present study was to obtain a rational explanation for the relationship between the overall anti-H. pylori efficacy and the CYP2C19 genotype. Methods. Six healthy volunteers were classified as extensive metabolizers and poor metabolizers, according to their CYP2C19 genotypes. Plasma concentrations and intragastric pH were monitored prior to and until 24 h after the administration of 20 mg omeprazole. The stability of amoxicillin, clarithromycin, and metronidazole was examined using buffer solutions with monitored intragastric pH, and their remaining percentage in the intragastric space was simulated. Results. The poor metabolizers, classified by the CYP2C19 geno-types, showed the higher effectiveness in anti-H pylori therapy, via the higher plasma concentration of omeprazole and the higher intragastric pH, and possibly the higher stability of antimicrobials in the higher intragastric pH. Conclusions. CYP2C19 genotyping is a very useful method to determine the effective and safe dosage regimen including the selection of the dual and triple therapy in anti-H. pylori therapy.

Original languageEnglish
Pages (from-to)615-621
Number of pages7
JournalPharmaceutical Research
Volume18
Issue number5
DOIs
Publication statusPublished - 2001

Fingerprint

Omeprazole
Genotype
Helicobacter pylori
Proton Pump Inhibitors
Pylorus
Plasmas
Clarithromycin
Amoxicillin
Metronidazole
Genetic Polymorphisms
Therapeutics
Polymorphism
Cytochrome P-450 CYP2C19
Healthy Volunteers
Buffers

Keywords

  • CYP2C19
  • Genotype
  • Helicobacter pylori
  • Intragastric pH
  • Omeprazole
  • Stability of antimicrobials

ASJC Scopus subject areas

  • Chemistry(all)
  • Pharmaceutical Science
  • Pharmacology

Cite this

CYP2C19 genotype related effect of omeprazole on intragastric pH and antimicrobial stability. / Kita, Tomoko; Tanigawara, Yusuke; Aoyama, Nobuo; Hohda, Takashi; Saijoh, Yoshie; Komada, Fusao; Sakaeda, Toshiyuki; Okumura, Katsuhiko; Sakai, Toshiyuki; Kasuga, Masato.

In: Pharmaceutical Research, Vol. 18, No. 5, 2001, p. 615-621.

Research output: Contribution to journalArticle

Kita, T, Tanigawara, Y, Aoyama, N, Hohda, T, Saijoh, Y, Komada, F, Sakaeda, T, Okumura, K, Sakai, T & Kasuga, M 2001, 'CYP2C19 genotype related effect of omeprazole on intragastric pH and antimicrobial stability', Pharmaceutical Research, vol. 18, no. 5, pp. 615-621. https://doi.org/10.1023/A:1011025125163
Kita, Tomoko ; Tanigawara, Yusuke ; Aoyama, Nobuo ; Hohda, Takashi ; Saijoh, Yoshie ; Komada, Fusao ; Sakaeda, Toshiyuki ; Okumura, Katsuhiko ; Sakai, Toshiyuki ; Kasuga, Masato. / CYP2C19 genotype related effect of omeprazole on intragastric pH and antimicrobial stability. In: Pharmaceutical Research. 2001 ; Vol. 18, No. 5. pp. 615-621.
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AU - Kita, Tomoko

AU - Tanigawara, Yusuke

AU - Aoyama, Nobuo

AU - Hohda, Takashi

AU - Saijoh, Yoshie

AU - Komada, Fusao

AU - Sakaeda, Toshiyuki

AU - Okumura, Katsuhiko

AU - Sakai, Toshiyuki

AU - Kasuga, Masato

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N2 - Purpose. A combination of proton pump inhibitors and antimicrobials has been applied as an anti-Helicobacter pylori (H. pylori) therapy. Omeprazole, one of the proton pump inhibitors, is metabolized by CYP2C19, which exhibits genetic polymorphism. It was reported previously that the overall anti-H, pylori efficacy can be related to the CYP2C19 genotype. The main aim of the present study was to obtain a rational explanation for the relationship between the overall anti-H. pylori efficacy and the CYP2C19 genotype. Methods. Six healthy volunteers were classified as extensive metabolizers and poor metabolizers, according to their CYP2C19 genotypes. Plasma concentrations and intragastric pH were monitored prior to and until 24 h after the administration of 20 mg omeprazole. The stability of amoxicillin, clarithromycin, and metronidazole was examined using buffer solutions with monitored intragastric pH, and their remaining percentage in the intragastric space was simulated. Results. The poor metabolizers, classified by the CYP2C19 geno-types, showed the higher effectiveness in anti-H pylori therapy, via the higher plasma concentration of omeprazole and the higher intragastric pH, and possibly the higher stability of antimicrobials in the higher intragastric pH. Conclusions. CYP2C19 genotyping is a very useful method to determine the effective and safe dosage regimen including the selection of the dual and triple therapy in anti-H. pylori therapy.

AB - Purpose. A combination of proton pump inhibitors and antimicrobials has been applied as an anti-Helicobacter pylori (H. pylori) therapy. Omeprazole, one of the proton pump inhibitors, is metabolized by CYP2C19, which exhibits genetic polymorphism. It was reported previously that the overall anti-H, pylori efficacy can be related to the CYP2C19 genotype. The main aim of the present study was to obtain a rational explanation for the relationship between the overall anti-H. pylori efficacy and the CYP2C19 genotype. Methods. Six healthy volunteers were classified as extensive metabolizers and poor metabolizers, according to their CYP2C19 genotypes. Plasma concentrations and intragastric pH were monitored prior to and until 24 h after the administration of 20 mg omeprazole. The stability of amoxicillin, clarithromycin, and metronidazole was examined using buffer solutions with monitored intragastric pH, and their remaining percentage in the intragastric space was simulated. Results. The poor metabolizers, classified by the CYP2C19 geno-types, showed the higher effectiveness in anti-H pylori therapy, via the higher plasma concentration of omeprazole and the higher intragastric pH, and possibly the higher stability of antimicrobials in the higher intragastric pH. Conclusions. CYP2C19 genotyping is a very useful method to determine the effective and safe dosage regimen including the selection of the dual and triple therapy in anti-H. pylori therapy.

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KW - Genotype

KW - Helicobacter pylori

KW - Intragastric pH

KW - Omeprazole

KW - Stability of antimicrobials

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