Comparison of the kinetic disposition of and serum gastrin change by lansoprazole versus rabeprazole during an 8-day dosing scheme in relation to CYP2C19 polymorphism

Ichiro Ieiri, Y. Kishimoto, H. Okochi, K. Momiyama, T. Morita, M. Kitano, T. Morisawa, Y. Fukushima, K. Nakagawa, J. Hasegawa, K. Otsubo, T. Ishizaki

研究成果: Contribution to journalArticle査読

59 被引用数 (Scopus)

抄録

Background: Little is known about differences in the disposition kinetics and pharmacological effects on gastrin levels between lansoprazole and rabeprazole given in a repeated dosing scheme with respect to the polymorphic CYP2C19. Aim: To provide preliminary information that should be considered when prescribing proton-pump inhibitors (PPIs) for the treatment of acid-related diseases with reference to the CYP2C19 genotypic status. Methods: Helicobacter pylori-negative healthy volunteers were divided into the following three groups (n=5 each) on the basis of genotyping for CYP2C19: homozygous (hmEMs) and heterozygous extensive metabolizers (htEMs), and poor metabolizers (PMs). All received once-daily 30-mg doses of lansoprazole or 10-mg doses of rabeprazole during an 8-day course in a crossover manner. Results: The relative values for the area under the serum concentration-time curve (AUC) of lansoprazole and rabeprazole in the hmEMs, htEMs, and PMs after the final doses were 1:1.7:3.9 and 1:1.7:3.8, respectively. The relative AUCs of gastrin in the hmEMs, htEMs, and PMs were 1.6:2.6:3.1 for lansoprazole and 1.6:2.6:2.9 for rabeprazole, respectively. Conclusion: The disposition kinetic behavior of the two PPIs is co-segregated with CYP2C19. The magnitude of CYP2C19-dependent drug availability in the systemic circulation and resulting gastrin response appears to be fairly similar between the two drugs within the same CYP2C19 genotypic groups after a multiple-dosing regimen.

本文言語英語
ページ(範囲)485-492
ページ数8
ジャーナルEuropean Journal of Clinical Pharmacology
57
5-6
出版ステータス出版済み - 2001
外部発表はい

All Science Journal Classification (ASJC) codes

  • 薬理学
  • 薬理学(医学)

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