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Effect of a rabeprazole half-dose twice daily on acid inhibition in patients with different CYP2C19 alleles

  • Pharmacodynamics
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Abstract

Purpose

Fractional doses of proton pump inhibitors (PPIs) more often than once daily (qd) inhibit 24-h acid secretion more effectively than an increase in the standard single daily dose. Although rabeprazole 5 mg qd is covered for prevention of aspirin-induced gastric injury under the Japanese insurance system, it is unclear whether rabeprazole 5 mg twice daily (bid) would more effectively inhibit acid secretion. We compared acid inhibition between rabeprazole 10 mg qd and 5 mg bid in healthy volunteers with different alleles of CYP2C19.

Methods

Twelve Helicobacter pylori-negative healthy volunteers (CYP2C19 genotypes: extensive metabolizer (EM) (n = 6) and poor metabolizer (PM) (n = 6)) received three kinds of regimen for 7 days under a randomized crossover design: rabeprazole 5 mg qd (5 mg QD), 10 mg qd (10 mg QD), and 5 mg bid (5 mg BID). A 24-hour pH monitoring was conducted before the trial and on day 7 of each regimen.

Results

No significant differences in median pH values (4.0 (1.9–5.9)) and (4.4 (2.1–6.5)) or percent time of pH ≥ 4 (50.7% (11.9–86.8%) and 56.8% (19.3–83.9%)) were seen between the 10 mg QD and 5 mg BID regimens. Median pHs and percent time of pH ≥ 4 in CYP2C19 PMs were significantly higher than those in EMs. With 5 mg BID, there was no significant difference in percent-time with pH ≥ 4 between daytime and nighttime, but the 10 mg QD showed a significant difference.

Conclusion

Rabeprazole 5 mg bid provided no therapeutic advantage for acid inhibition compared with rabeprazole 10 mg qd, regardless of CYP2C19 genotype status.

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Acknowledgments

We thank Libby Cone, MD, MA, from DMC Corp. (www.dmed.co.jp <http://www.dmed.co.jp/>) for editing drafts of this manuscript.

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Authors and Affiliations

  1. Department of Gastroenterology, National Hospital Organization, Kyoto Medical Center, Kyoto, 612-8555, Japan

    Masaki Murata

  2. Department of Gastroenterological Endoscopy, Tokyo Medical University Hospital, 6-7-1, Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan

    Mitsushige Sugimoto

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  1. Masaki Murata
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Correspondence to Mitsushige Sugimoto.

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Murata, M., Sugimoto, M. Effect of a rabeprazole half-dose twice daily on acid inhibition in patients with different CYP2C19 alleles. Eur J Clin Pharmacol 76, 1253–1261 (2020). https://doi.org/10.1007/s00228-020-02917-w

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  • DOI: https://doi.org/10.1007/s00228-020-02917-w

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