CYP2C19 genotype status and intragastric pH during dosing with lansoprazole or rabeprazole.
BACKGROUND
CYP2C19 has an important role in the catabolism of several proton pump inhibitors. However, the relative contribution of CYP2C19-mediated metabolism varies among the different proton pump inhibitors.


OBJECTIVE
To determine the effect of CYP2C19 genotype status on intragastric pH during dosing with lansoprazole or rabeprazole.


METHODS
The subjects were 20 male volunteers without Helicobacter pylori infection. Their CYP2C19 genotype status was determined by a polymerase chain reaction-restriction fragment length polymorphism method. Twenty-four-hour monitoring of intragastric acidity was performed three times: once without medication, once on the last day of a 7-day course of rabeprazole, and once on the last day of a 7-day course of lansoprazole.


RESULTS
Subjects were divided into three groups on the basis of their CYP2C19 genotype status: homozygous extensive metabolizers (homo-EMs, n=7), heterozygous extensive metabolizers (hetero-EMs, n=9), and poor metabolizers (PMs, n=4). The median pH during rabeprazole administration was not influenced by CYP2C19 genotype. On the other hand, the median pH in PMs during lansoprazole dosing was higher than in homo-EMs and hetero-EMs. The percentage of time with pH < 4.0 had a similar tendency to that of median pH.


CONCLUSIONS
CYP2C19 genotype status influences gastric acid suppression by lansoprazole, but not by rabeprazole.
Adachi
K
K
Department of Internal Medicine II, Shimane Medical University, Izumo, Shimane, Japan. kadachi@shimane-med.ac.jp
Katsube
T
T
Kawamura
A
A
Takashima
T
T
Yuki
M
M
Amano
K
K
Ishihara
S
S
Fukuda
R
R
Watanabe
M
M
Kinoshita
Y
Y
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000328:Adult; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases; D001562:Benzimidazoles / Q000494:pharmacology*; D065731:Cytochrome P-450 CYP2C19; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005744:Gastric Acid / Q000378:metabolism / Q000502:physiology*; D005745:Gastric Acidity Determination; D005838:Genotype; D006801:Humans; D006863:Hydrogen-Ion Concentration; D064747:Lansoprazole; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000494:pharmacology; D012150:Polymorphism, Restriction Fragment Length; D054328:Proton Pump Inhibitors; D064750:Rabeprazole
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D054328:Proton Pump Inhibitors; D064747:Lansoprazole; D064750:Rabeprazole; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole