CYP2C19 genotype and pharmacokinetics of three proton pump inhibitors in healthy subjects

Toshiyuki Sakai, Nobuo Aoyama, Tomoko Kita, Toshiyuki Sakaeda, Kohshi Nishiguchi, Yukari Nishitora, Takashi Hohda, Daisuke Sirasaka, Takao Tamura, Yusuke Tanigawara, Masato Kasuga, Katsuhiko Okumura

研究成果: Article

111 引用 (Scopus)

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Purpose. To predict the CYP2C19 genotype-dependence in anti-Helicobacter pylori (H. pylori) therapy when lansoprazole or rabeprazole was used instead of omeprazole as a proton pump inhibitor (PPI). Methods. A comparative pharmacokinetic study with each PPI was designed as an open, randomized, and crossover study of 18 Japanese healthy volunteers who were classified into the homozygous, heterozygous extensive metabolizer and the poor metabolizer based on the CYP2C19 genotype determined by PCR-RFLP method. Each subject received a single oral dose of 20 mg omeprazole, 30 mg lansoprazole, or 20 mg sodium rabeprazole, with at least 1 week washout period between treatments. Plasma concentrations of PPIs and their metabolites were monitored until 12 h after medication. Results. Pharmacokinetic profiles of omeprazole and lansoprazole were well correlated with the CYP2C19 genotype. The heterozygous extensive metabolizer was slightly different from the homozygote, but there was no statistically significant difference. The CYP2C19 genotype dependence found for lansoprazole was not obvious compared with omeprazole. As for rabeprazole, the pharmacokinetic profile was independent of the CYP2C19 genotype. Conclusions. CYP2C19 genotype dependence will be found in the anti-H. pylori therapy even when lansoprazole is used as the PPI.

元の言語English
ページ(範囲)721-727
ページ数7
ジャーナルPharmaceutical research
18
発行部数6
DOI
出版物ステータスPublished - 2001 9 5

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

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    Sakai, T., Aoyama, N., Kita, T., Sakaeda, T., Nishiguchi, K., Nishitora, Y., Hohda, T., Sirasaka, D., Tamura, T., Tanigawara, Y., Kasuga, M., & Okumura, K. (2001). CYP2C19 genotype and pharmacokinetics of three proton pump inhibitors in healthy subjects. Pharmaceutical research, 18(6), 721-727. https://doi.org/10.1023/A:1011035007591