Tailored Treatment of H. Pylori Infection Based Polymorphisms of CYP2C19 and 23S rRNA of H. Pylori
Tailored Treatment of H. Pylori Infection Based Polymorphisms of CYP2C19 and 23S rRNA of H. Pylori
The eradication rate of the standard H. pylori eradication therapy (such as the triple
 therapy with a proton pump inhibitor [PPI], amoxicillin and clarithromycin) depends on
 bacterial susceptibility to clarithromycin and genotypes of CYP2C19 in patients. The
 investigators intend to investigate whether the tailored therapy based on the two
 above-mentioned factors increases the cure rate of the initial eradication therapy.
Current treatment strategies for the eradication of H. pylori include a proton pump inhibitor
 (PPI) and one or two anti-bacterial agents, such as amoxicillin, clarithromycin, and
 metronidazole.

 PPIs, such as lansoprazole and omeprazole, are mainly metabolized in the liver by a
 genetically determined enzyme, S-mephenytoin 4'-hydroxylase (CYP2C19). Plasma concentrations
 of PPIs and their activity for acid inhibition depend to a significant extent on the genetic
 differences in the activity of this enzyme. The acid inhibition attained by the standard dose
 of a PPI is sometimes therapeutically insufficient in individuals with the rapid extensive
 metabolizer (RM) genotype of CYP2C19, whereas that in individuals with poor metabolizer (PM)
 genotype of CYP2C19 is in most cases clinically sufficient. We have reported that the CYP2C19
 genotype status is one of the determinants of H. pylori eradication therapy. In the triple
 therapy with a PPI, amoxicillin, and clarithromycin, bacterial susceptibility to
 clarithromycin as well as the CYP2C19 genotype status was significantly related to
 eradication rates of H. pylori. Therefore, the tailored treatment based on these two factors
 is expected to increase the eradication rates of the initial therapy.

 Interestingly, both of CYP2C19 genotypes and bacterial susceptibility to clarithromycin can
 be measured by the genetic test of the single nucleotide polymorphisms (SNPs) of the CYP2C19
 gene and the 23S rRNA gene of H. pylori, respectively. We have recently developed the
 inexpensive and reliable high-throughput method for measurement of such SNPs by the invader
 assay. Polymorphisms of CYP2C19 of patients and mutations of 23S rRNA of H. pylori associated
 with susceptibility to clarithromycin can be detected from the gastric tissue samples
 infected with H. pylori, such as the gastric tissue sample already used for rapid urease test
 (RUT).

 Then, we treat H. pylori-positive patients by the tailored regimen based on genotypes of
 CYP2C19 of patients and 23S rRNA of H. pylori or the standard regimen and test the
 therapeutic efficacy of this pharmacogenomics-based tailored strategy in a prospective
 manner.

 Patients were randomly assigned to the standard or tailored regimen group with the use of a
 computer-generated randomization list based on a blocked randomization method.

 Patients assigned to the standard regimen group were treated with 30 mg of lansoprazole bid,
 400 mg of clarithromycin bid, and 750 mg of amoxicillin bid for one week, which had been
 approved under the Japanese formulary regulation regardless of any pharmacogenomic
 backgrounds of H. pylori-infected peptic ulcer patients.

 In the tailored regimen group, patients infected with a clarithromycin-sensitive strain of H.
 pylori are treated with triple therapy consisting of clarithromycin 200 mg tid, amoxicillin
 500 mg tid and the individualized doses of lansoprazole dose (i.e., 30 mg tid in RMs, 15 mg
 tid in IMs, and 15 mg bid in PMs) for one week, while patients infected with a
 clarithromycin-resistant strain of H. pylori are treated with dual therapy consisting of
 amoxicillin 500 mg qid and the individualzed dose of lansoprazole (i.e., 30 mg qid in RMs, 15
 mg qid in IMs, and 15 mg bid in PMs) for two weeks.
Inclusion Criteria:

 -  Patients with H. pylori infection

 Exclusion Criteria:

 -  Patients without H. pylori infection