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CYP2C19 Genotype and Pharmacokinetics of Three Proton Pump Inhibitors in Healthy Subjects

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Abstract

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.

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Author notes

  1. Yusuke Tanigawara

    Present address: Department of Hospital Pharmacy, School of Medicine, Keio University, Shinjuku-ku, Tokyo, 160-8582, Japan

Authors and Affiliations

  1. Second Department of Internal Medicine, School of Medicine, Kobe University, Chuo-ku, Kobe, 650-0017, Japan

    Toshiyuki Sakai, Nobuo Aoyama, Daisuke Sirasaka, Takao Tamura & Masato Kasuga

  2. Department of Endoscopy, School of Medicine, Kobe University, Chuo-ku, Kobe, 650-0017, Japan

    Nobuo Aoyama, Toshiyuki Sakaeda, Kohshi Nishiguchi, Yukari Nishitora & Takashi Hohda

  3. Department of Hospital Pharmacy, School of Medicine, Kobe University, Chuo-ku, Kobe, 650-0017, Japan

    Tomoko Kita, Yusuke Tanigawara & Katsuhiko Okumura

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Sakai, T., Aoyama, N., Kita, T. et al. CYP2C19 Genotype and Pharmacokinetics of Three Proton Pump Inhibitors in Healthy Subjects. Pharm Res 18, 721–727 (2001). https://doi.org/10.1023/A:1011035007591

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