Effects of CYP2C19 gene polymorphism on cure rates for Helicobacter pylori infection by triple therapy with proton pump inhibitor (omeprazole or rabeprazole), amoxycillin and clarithromycin in Japan.
BACKGROUND
Omeprazole is mainly metabolized by cytochrome P450 2C19 (CYP2C19) in the liver. Rabeprazole, on the other hand, is mainly metabolized to thioether-rabeprazole via a non-enzymatic pathway and partially metabolized to demethylated-rabeprazole by CYP2C19 in liver CYP2C19 status may affect cure rate for Helicobacter pylori infection with proton pump inhibitor triple therapy.


OBJECTIVE
To investigate whether genetic polymorphism of CYP2C19 and selected proton pump inhibitors (omeprazole or rabeprazole) were associated with cure rate for Helicobacter pylori infection using triple therapy with omeprazole or rabeprazole, amoxicillin, and clarithromycin.


METHODS
A total of 170 Helicobacter pylori-positive patients with chronic gastritis were randomized to receive one of the following Helicobacter pylori eradication regimens; OAC (omeprazole 20 mg bd, amoxycillin 750 mg bd and clarithromycin 400 mg bd for 1 week) and RAC (rabeprazole 20 mg bd, amoxycillin 750 mg bd and clarithromycin 400 mg bd for 1 week). The CYP2C19 genotype; wild-type or two mutant genes (ml in exon 5 and m2 in exon 4), or both, were identified by polymerase chain reaction-restriction fragment length polymorphism.


RESULTS
In DAC regimen, cure rate (per protocol analysis) was 73.3% in homozygous extensive metabolizers, 86.1% in heterozygous extensive metabolizers, and 85.0% in poor metabolizers. In RAC regimen, the cure rate was 81.0% in homozygous extensive metabolizers, 82.9% in heterozygous extensive metabolizers, and 87.5% in poor metabolizers. Cure rate was not significantly different between the CYP2C19 genotypes in both regimens.


CONCLUSIONS
Triple therapy with proton pump inhibitor (omeprazole or rabeprazole), amoxycillin, and clarithromycin is sufficiently effective in cure of Helicobacter pylori infection regardless of CYP2C19 status.
Dojo
M
M
Second Department of Internal Medicine, Fukui Medical University, Japan.
Azuma
T
T
Saito
T
T
Ohtani
M
M
Muramatsu
A
A
Kuriyama
M
M
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000328:Adult; D000658:Amoxicillin / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases; D001562:Benzimidazoles / Q000627:therapeutic use*; D017291:Clarithromycin / Q000627:therapeutic use; D065731:Cytochrome P-450 CYP2C19; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004359:Drug Therapy, Combination; D005260:Female; D005756:Gastritis / Q000188:drug therapy / Q000382:microbiology; D005838:Genotype; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000235:genetics; D016480:Helicobacter pylori; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D009853:Omeprazole / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D006180:Proton-Translocating ATPases / Q000627:therapeutic use*; D064750:Rabeprazole; D016896:Treatment Outcome
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D001562:Benzimidazoles; D064750:Rabeprazole; 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; D006180:Proton-Translocating ATPases; D017291:Clarithromycin; D009853:Omeprazole