Effect of genotypic differences in CYP2C19 on cure rates for Helicobacter pylori infection by triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin.
BACKGROUND
Proton pump inhibitors such as omeprazole and lansoprazole are mainly metabolized by CYP2C19 in the liver. The therapeutic effects of proton pump inhibitors are assumed to depend on CYP2C19 genotype status.


OBJECTIVE
We investigated whether CYP2C19 genotype status was related to eradication rates of H pylori by triple proton pump inhibitor-clarithromycin-amoxicillin (INN, amoxicilline) therapy and attempted to establish a strategy for treatment after failure to eradicate H pylori.


METHODS
A total of 261 patients infected with H pylori completed initial treatment with 20 mg of omeprazole or 30 mg of lansoprazole twice a day, 200 mg of clarithromycin three times a day, and 500 mg of amoxicillin three times a day for 1 week. CYP2C19 genotypes of patients were determined with polymerase chain reaction-restriction fragment length polymorphism analysis. Patients without eradication after initial treatment were retreated with 30 mg of lansoprazole four times daily and 500 mg of amoxicillin four times daily for 2 weeks.


RESULTS
Eradication rates for H pylori were 72.7% (95% confidence interval, 64.4%-81.8%), 92.1% (confidence interval, 86.4%-97.3%), and 97.8% (confidence interval, 88.5%-99.9%) in the homozygous extensive, heterozygous extensive, and poor metabolizer groups, respectively. Thirty-four of 35 patients without eradication had an extensive metabolizer genotype of CYP2C19. Nineteen of those patients were infected with clarithromycin-resistant strains of H pylori. However, there were no amoxicillin-resistant strains of H pylori. Re-treatment of H pylori infection with dual high-dose lansoprazole-amoxicillin therapy succeeded in 30 of 31 patients with extensive metabolizer genotype of CYP2C19.


CONCLUSIONS
The majority of patients without initial eradication of H pylori had an extensive metabolizer CYP2C19 genotype but were successfully re-treated with high doses of lansoprazole and an antibiotic to which H pylori was sensitive, such as amoxicillin, even when the patients were infected with clarithromycin-resistant strains of H pylori.
First Department of Medicine, Hamamatsu University School of Medicine, Japan. furuta@akiha.hama-med.ac.jp
T
T
Furuta
N
N
Shirai
M
M
Takashima
F
F
Xiao
H
H
Hanai
H
H
Sugimura
K
K
Ohashi
T
T
Ishizaki
E
E
Kaneko
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000658:Amoxicillin / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D001189:Aryl Hydrocarbon Hydroxylases; D017291:Clarithromycin / Q000627:therapeutic use*; D065731:Cytochrome P-450 CYP2C19; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000235:genetics*; D004359:Drug Therapy, Combination; D004381:Duodenal Ulcer / Q000188:drug therapy*; D005260:Female; D005838:Genotype; D016481:Helicobacter Infections / Q000188:drug therapy*; D016480:Helicobacter pylori; D006801:Humans; D064747:Lansoprazole; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000187:drug effects / Q000235:genetics*; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D010406:Penicillins / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D016896:Treatment Outcome
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000900:Anti-Bacterial Agents; D000897:Anti-Ulcer Agents; D010406:Penicillins; D064747:Lansoprazole; D000658:Amoxicillin; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D017291:Clarithromycin; D009853:Omeprazole