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One-day front-loading with four doses of rabeprazole followed by a standard twice-daily regimen provides sufficient acid inhibition in extensive metabolizers of CYP2C19

  • Pharmacodynamics
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Abstract

Background

Four times daily dosing (qid) with a proton pump inhibitor can cause rapid increase in intragastric pH. We investigated the efficacy of the front-loading with rabeprazole 10 mg qid on a subsequent regimen with rabeprazole 10 mg twice daily (bid) for 7 days in extensive metabolizers (EMs) of CYP2C19.

Methods

Five EMs received three different 1-week regimens in a crossover manner as follows: (1) rabeprazole 10 mg bid for 7 days; (2) a front-loading regimen of rabeprazole (rabeprazole 10 mg qid on day 0 and bid on days 1 to 7); and (3) rabeprazole 10 mg qid for 7 days. Five intermediate metabolizers (IMs) and four poor metabolizers (PMs) received rabeprazole 10 mg bid regimen only. Twenty-four-hour intragastric pH-monitorings were performed on days 1, 4, and 7. Area under the intragastric pH-time curves (AUCs) from days 1 to 7 was calculated using 24-h median intragastric pHs on days 1, 4, and 7.

Results

Twenty-four-hour intragastric pHs in the front-loading group on days 1, 4, and 7 were 5.1, 4.9, and 5.1, respectively. The median AUC with front-loading in EMs (34.4, pH·day) was significantly higher than that in EMs with rabeprazole 10 mg bid (30.74, p = 0.043). No statistically significant differences in median AUCs were noted among front-loading in EMs, rabeprazole 10 mg qid in EMs (37.2), rabeprazole 10 mg bid in IMs (37.3), and PMs (39.4).

Conclusions

The one-day front-loading regimen of rabeprazole 10 mg qid provided sufficient acid inhibition for 7 days, even in CYP2C19 EMs.

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Abbreviations

EM:

Extensive metabolizer

H. pylori :

Helicobacter pylori

IM:

Intermediate metabolizer

PPI:

Proton pump inhibitor

PM:

Poor metabolizer

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Conflicts of interest

The First Department of Medicine and the Center for Clinical Research at Hamamatsu University School of Medicine have received grants from Takeda Pharmaceutical Co., Ltd., AstraZeneca KK, Eisai Co., Ltd., and Daiichi-Sankyo Co. Ltd. The authors have no other conflicts of interest that are directly relevant to the content of this article.

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Authors and Affiliations

  1. First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan

    Takuma Kagami, Mitsushige Sugimoto, Hitomi Ichikawa, Shu Sahara, Takahiro Uotani, Mihoko Yamade, Yasushi Hamaya, Ken Sugimoto & Hiroaki Miyajima

  2. Department of Clinical Oncology, Hamamatsu University School of Medicine, Hamamatsu, Japan

    Moriya Iwaizumi

  3. Department of Endoscopic and Photodynamic Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan

    Satoshi Osawa

  4. Center for Clinical Research, Hamamatsu University School of Medicine, 1-20-1, Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan

    Takahisa Furuta

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  1. Takuma Kagami
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Correspondence to Takahisa Furuta.

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Kagami, T., Sugimoto, M., Ichikawa, H. et al. One-day front-loading with four doses of rabeprazole followed by a standard twice-daily regimen provides sufficient acid inhibition in extensive metabolizers of CYP2C19. Eur J Clin Pharmacol 71, 1467–1475 (2015). https://doi.org/10.1007/s00228-015-1941-9

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  • DOI: https://doi.org/10.1007/s00228-015-1941-9

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