Treatment strategy to eradicate Helicobacter pylori infection: impact of pharmacogenomics-based acid inhibition regimen and alternative antibiotics.
The eradication rates of Helicobacter pylori by the triple therapy consisting of a proton pump inhibitor (PPI) and two antimicrobial agents are mainly influenced by bacterial susceptibility to antimicrobial agents and magnitude of acid inhibition during the treatment with a PPI. Acid inhibition during the treatment is affected by the dosing schemes of acid inhibitory drugs (i.e., PPI), genotypes of drug-metabolizing enzymes (i.e., CYP450 2C19), drug transporters (i.e., multi-drug resistant transporter-1) and inflammatory cytokines (i.e., IL-1 beta). Modification of dosing schedules of a PPI, such as frequent PPI dosing and concomitant dosing with a histamine 2-receptor antagonist, could overcome these genetics-related differences in therapeutic effectiveness. For attaining higher eradication rates, the tailored regimen based on the relevant pharmacogenomics is preferable.
Sugimoto
Mitsushige
M
Hamamatsu University School of Medicine, First Department of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan. mitsu@hama-med.ac.jp
Furuta
Takahisa
T
Shirai
Naohito
N
Kodaira
Chise
C
Nishino
Masafumi
M
Yamade
Mihoko
M
Ikuma
Mutsuhiro
M
Watanabe
Hiroshi
H
Ohashi
Kyoichi
K
Hishida
Akira
A
Ishizaki
Takashi
T
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000897:Anti-Ulcer Agents / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D065731:Cytochrome P-450 CYP2C19; D016207:Cytokines / Q000235:genetics; D024881:Drug Resistance, Bacterial; D005744:Gastric Acid / Q000378:metabolism; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D016480:Helicobacter pylori; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D054328:Proton Pump Inhibitors
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000900:Anti-Bacterial Agents; D000897:Anti-Ulcer Agents; D016207:Cytokines; D054328:Proton Pump Inhibitors; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19