Therapeutic impact of CYP2C19 pharmacogenetics on proton pump inhibitor-based eradication therapy for Helicobacter pylori.
Current regimens for the eradication of Helicobacter pylori consist of a proton pump inhibitor (PPI) plus one or two antibacterial agents, such as amoxicillin (AMPC), clarithromycin (CAM) or metronidazole (MNZ). PPIs are mainly metabolized by S-mephenytoin 4'-hydroxylase (CYP2C19) in the liver. The polymorphism of CYP2C19 is associated with the pharmacokinetics and pharmacodynamics of PPIs. Eradication rates by PPI-based therapies are also affected by this genotype, as well as bacterial resistance to antibiotics. An individualized treatment strategy based on CYP2C19-related pharmacogenetics or pharmacogenomics and bacterial resistance is expected to increase the cure rate of the initial treatment. It is also necessary to recognize that there is a possible drug-drug interaction between some of the drugs used in this treatment regimen.
First Department of Medicine, Department of Clinical Laboratories, Hamamatsu University School of Medicine, Hamamatsu, Japan. furuta@hama-med.ac.jp
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Furuta
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Shirai
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Ohashi
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Ishizaki
D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D002986:Clinical Trials as Topic; D065731:Cytochrome P-450 CYP2C19; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005765:Gastrointestinal Agents / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D005838:Genotype; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000201:enzymology; D016480:Helicobacter pylori / Q000235:genetics*; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D054328:Proton Pump Inhibitors
D000900:Anti-Bacterial Agents; D005765:Gastrointestinal Agents; D054328:Proton Pump Inhibitors; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19