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Individualized Therapy for Gastroesophageal Reflux Disease

Potential Impact of Pharmacogenetic Testing based on CYP2C19

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Abstract

The main therapeutic agent for gastroesophageal reflux disease (GERD) is a proton pump inhibitor (PPI). Plasma levels and the acid inhibitory effect of PPIs depend on the activity of cytochrome P450 (CYP) 2C19, which is polymorphic. Genotypes of CYP2C19 are classified into three groups: rapid metabolizers (RMs: *1/*1), intermediate metabolizers (IMs: *1/*X), and poor metabolizers (PMs: *X/*X), where *1 and X represent the wild type and the mutant allele, respectively. RMs include ultra-rapid metabolizers, who possess the CYP2C19*17 allele. The pharmacokinetics and pharmacodynamics of PPIs differ among different CYP2C19 genotype groups. Plasma PPI levels and intragastric pH values during PPI treatment are lowest in the RM group, intermediate in the IM group, and highest in the PM group. These CYP2C19-genotype-dependent differences in the pharmacokinetics and pharmacodynamics of PPIs influence the healing and recurrence of GERD during PPI treatment, suggesting the need for CYP2C19 genotype-based tailored therapy for GERD. CYP2C19 pharmacogenetics should be taken into consideration for the personalization of PPI-based therapy. However, the clinical usefulness of CYP2C19 genotype testing in GERD therapy should be verified in clinical studies.

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Acknowledgments

The Center for Clinical Research at Hamamatsu University School of Medicine has received grants from Takeda Pharmaceutical Co., Ltd., AstraZeneca KK, and Eisai Co., Ltd., and Drs. Furuta and Sugimoto have received lecture fees from those companies. 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. Center for Clinical Research, Hamamatsu University School of Medicine, 1-20-1, Handa-Yama, Higashi-Ku, Hamamatsu, 431-3192, Japan

    Takahisa Furuta

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

    Mitsushige Sugimoto

  3. Department of Gastroenterology, JA Shizuoka Kohseiren Enshu Hospital, Hamamatsu, Japan

    Naohito Shirai

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  1. Takahisa Furuta
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  2. Mitsushige Sugimoto
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  3. Naohito Shirai
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Correspondence to Takahisa Furuta.

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Furuta, T., Sugimoto, M. & Shirai, N. Individualized Therapy for Gastroesophageal Reflux Disease. Mol Diagn Ther 16, 223–234 (2012). https://doi.org/10.1007/BF03262211

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