Influence of CYP2C19 pharmacogenetic polymorphism on proton pump inhibitor-based therapies.
Proton pump inhibitors (PPIs), such as omeprazole, lansoprazole, rabeprazole, esomeprazole, and pantoprazole, are mainly metabolized by CYP2C19 in the liver. There are genetically determined differences in the activity of this enzyme. The genotypes of CYP2C19 are classified into the three groups, rapid extensive metabolizer (RM), intermediate metabolizer (IM), and poor metabolizer (PM). The pharmacokinetics and pharmacodynamics of PPIs depend on CYP2C19 genotype status. Plasma PPI levels and intragastric pHs during PPI treatment in the RM group are lowest, those in the IM group come next, and those in the PM group are highest of the three groups. These CYP2C19 genotype-dependent differences in pharmacokinetics and pharmacodynamics of PPIs influence the cure rates for the gastro-esophageal reflux disease and H. pylori infection by PPI-based therapies. For the better PPI-based treatment, doses and dosing schemes of PPIs should be optimized based on CYP2C19 genotype status.
First Department of Medicine, Hamamatsu University School of Medicine. furuta@hama-med.ac.jp
Takahisa
T
Furuta
Naohito
N
Shirai
Mitsushige
M
Sugimoto
Akiko
A
Nakamura
Akira
A
Hishida
Takashi
T
Ishizaki
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000658:Amoxicillin / Q000009:adverse effects / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D001562:Benzimidazoles / Q000493:pharmacokinetics / Q000627:therapeutic use; D017291:Clarithromycin / Q000009:adverse effects / Q000627:therapeutic use; D065731:Cytochrome P-450 CYP2C19; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D064098:Esomeprazole; D005764:Gastroesophageal Reflux / Q000188:drug therapy; D005838:Genotype; D016481:Helicobacter Infections / Q000178:diet therapy; D016480:Helicobacter pylori; D006801:Humans; D064747:Lansoprazole; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism; D009853:Omeprazole / Q000031:analogs & derivatives / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D054328:Proton Pump Inhibitors; D064750:Rabeprazole
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D054328:Proton Pump Inhibitors; D064747:Lansoprazole; D064750:Rabeprazole; D000658:Amoxicillin; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D017291:Clarithromycin; D009853:Omeprazole; D064098:Esomeprazole