CYP2C19 genotype status and effect of omeprazole on intragastric pH in humans.
OBJECTIVE
Omeprazole is metabolized by genetically determined S-mephenytoin 4'-hydroxylase (CYP2C19) in the liver. This study aimed to determine whether the effect of omeprazole on intragastric pH depends on CYP2C19 genotype status.


METHODS
CYP2C19 genotype status for 2 mutations associated with the poor metabolizer phenotype was determined by a polymerase chain reaction-restriction fragment length polymorphism method in 16 healthy volunteers. Helicobacterpylori status was determined by serology and the [13C]urea breath test. After a single oral administration of 20 mg omeprazole or a placebo, intragastric pH values were recorded for 24 hours. Plasma levels of omeprazole and its 2 metabolites and gastrin were measured before and 1, 2, 3, 5, 7, 10, and 24 hours after administration.


RESULTS
Fifteen of the 16 subjects were H pylori negative. Five of the 15 subjects were homozygous extensive metabolizers, 4 were heterozygous extensive metabolizers, and 6 were poor metabolizers. After omeprazole administration, significant differences in mean intragastric pH values and plasma levels of gastrin, omeprazole and its metabolites were observed among the 3 groups, whereas no significant differences in these parameters were observed with the placebo administration.


CONCLUSIONS
The effect of omeprazole on intragastric pH significantly depends on CYP2C19 genotype status. The genotyping test of CYP2C19 may be useful for an optimal prescription of omeprazole.
Furuta
T
T
First Department of Medicine, Hamamatsu University School of Medicine, Japan.
Ohashi
K
K
Kosuge
K
K
Zhao
X J
XJ
Takashima
M
M
Kimura
M
M
Nishimoto
M
M
Hanai
H
H
Kaneko
E
E
Ishizaki
T
T
D000328:Adult; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases; D044466:Asian People / Q000235:genetics; D065731:Cytochrome P-450 CYP2C19; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D005755:Gastrins / Q000097:blood*; D005838:Genotype; D016481:Helicobacter Infections / Q000378:metabolism / Q000382:microbiology; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007564:Japan; D008297:Male; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors* / Q000235:genetics*; D009853:Omeprazole / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012016:Reference Values; D013270:Stomach / Q000382:microbiology
D000897:Anti-Ulcer Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D005755:Gastrins; 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