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CYP2C19 genotype is associated with symptomatic recurrence of GERD during maintenance therapy with low-dose lansoprazole

  • Pharmacogenetics
  • Published:
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Abstract

Background/aims

Maintenance therapy of gastroesophageal reflux disease (GERD) is usually performed with a low dose of a proton-pump inhibitor (PPI). Because PPIs are metabolized by CYP2C19 in the liver, we investigated whether a patient’s CYP2C19 genotype was associated with symptomatic recurrence of GERD during maintenance therapy with a low dose of a PPI.

Methods

We enrolled 124 patients with erosive GERD whose esophageal mucosal breaks were endoscopically proven to be cured after treatment with lansoprazole 30 mg/day for 8 weeks. When reflux symptoms occurred less than once per week, the dose of lansoprazole was decreased to 15 mg/day, but if symptoms then occurred more than once per week, it was restored to 30 mg/day. CYP2C19 genotypes were classified as rapid metabolizer (RM), intermediate metabolizer (IM) or poor metabolizer (PM).

Results

In 18 of 54 RMs, 28 of 56 IMs, and 8 of 14 PMs, the maintenance dose of lansoprazole was decreased to 15 mg/day, but in 16 (88.9%), 22 (78.6%), and 4 (50%), respectively, there was symptomatic recurrence of GERD and the dose was restored to 30 mg/day. The hazard ratios of symptomatic recurrence of GERD in IMs and PMs compared with RMs were 0.40 (95%CI: 0.19–0.87, P = 0.021) and 0.19 (95%CI: 0.05–0.69, P = 0.011).

Conclusion

When the dose of lansoprazole is decreased, the RM genotype of CYP2C19 appears to be a risk factor for symptomatic recurrence of GERD. The CYP2C19 genotyping test would be useful for determining the optimal dose of a PPI for maintenance therapy of GERD.

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Abbreviations

CYP:

Cytochrome P450

GERD:

Gastroesophageal reflux disease

IM:

Intermediate metabolizer

PM:

Poor metabolizer

PPI:

Proton-pump inhibitor

RM:

Rapid metabolizer

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Acknowledgements

This work was supported by a grant-in-aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan (20590718).

Conflict of interest

None of the authors had any conflicts of interest related to this study.

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Authors and Affiliations

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

    Takahisa Furuta

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

    Mitsushige Sugimoto, Chise Kodaira, Masafumi Nishino, Mihoko Yamade, Mutsuhiro Ikuma & Akira Hishida

  3. Department of Gastroenterology, Enshu General Hospital, Hamamatsu, Japan

    Naohito Shirai

  4. Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, Hamamatsu, Japan

    Hiroshi Watanabe

  5. Department of Pharmacology, Hamamatsu University School of Medicine, Hamamatsu, Japan

    Kazuo Umemura

  6. Department of Medical Informatics, Hamamatsu University School of Medicine, Hamamatsu, Japan

    Michio Kimura

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  1. Takahisa Furuta
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  2. Mitsushige Sugimoto
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Correspondence to Takahisa Furuta.

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Furuta, T., Sugimoto, M., Kodaira, C. et al. CYP2C19 genotype is associated with symptomatic recurrence of GERD during maintenance therapy with low-dose lansoprazole. Eur J Clin Pharmacol 65, 693–698 (2009). https://doi.org/10.1007/s00228-009-0628-5

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  • DOI: https://doi.org/10.1007/s00228-009-0628-5

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