CYP2C19 pharmacogenomics associated with therapy of Helicobacter pylori infection and gastro-esophageal reflux diseases with a proton pump inhibitor

Author:

Furuta Takahisa1,Sugimoto Mitsushige2,Shirai Naohito3,Ishizaki Takashi4

Affiliation:

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

2. Hamamatsu University School of Medicine, First Department of Medicine, 1-20-1, Handa-Yama, Higashi-Ku, Hamamatsu, 431-3192, Japan

3. Hamamatsu University School of Medicine, Department of Gastroenterology, 1-20-1, Handa-Yama, Higashi-Ku, Hamamatsu, 431-3192, Japan

4. Hamamatsu University School of Medicine, Department of Clinical Pharmacology and Therapeutics, 1-20-1, Handa-Yama, Kita-Ku, Hamamatsu, 431-3192, Japan

Abstract

Proton pump inhibitors (PPIs), such as omeprazole, lansoprazole and rabeprazole, are metabolized by CYP2C19 in the liver. There are genetic differences in the activity of this enzyme. Genotypes of CYP2C19 are classified into three groups, rapid metabolizer (RM: *1/*1), intermediate metabolizer (IM: *1/*X) and poor metabolizer (PM: *X/*X) (*1 and ‘X’ represent the wild-type and mutant allele, respectively). The pharmacokinetics and pharmacodynamics of PPIs differ among three different CYP2C19 genotype groups. Plasma PPI levels and intragastric pHs during PPI treatment in the RM group are lowest, those in the IM group come next, and those in the PM group are highest of the three groups. These CYP2C19 genotypic differences in pharmacokinetics and pharmacodynamics of PPIs influence the healing and eradication rates for the gastro-esophageal reflux disease and Helicobacter pylori infection by PPI-based regimens. Recently, the CYP2C19 genotype-based tailored therapy for H. pylori infection has been found to be effective. CYP2C19 pharmacogenetics should be taken into consideration for the personalization of a PPI-based therapy.

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

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