Objective: Omeprazole is metabolized by genetically determined S-mephenytoi
n 4'-hydroxylase (CYP2C19) in the liver. This study aimed to determine whet
her the effect of omeprazole on intragastric pH depends on CYP2C19 genotype
Methods: CYP2C19 genotype status for 2 mutations associated with the poor m
etabolizer phenotype was determined by a polymerase chain reaction-restrict
ion fragment length polymorphism method in 16 healthy volunteers. Helicobac
ter pylori status was determined by serology and the [C-13]urea breath test
. After a single oral administration of 20 mg omeprazole or a placebo, intr
agastric 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, 1
0, and 24 hours after administration.
Results:Fifteen of the 16 subjects were H pylori negative. Five of the 15 s
ubjects were homozygous extensive metabolizers, 4 were heterozygous extensi
ve metabolizers, and 6 were poor metabolizers. After omeprazole administrat
ion, significant differences in mean intragastric PH values and plasma leve
ls of gastrin, omeprazole and its metabolites were observed among the 3 gro
ups, whereas no significant differences in these parameters were observed w
ith the placebo administration.
Conclusions: The effect of omeprazole on intragastric pH significantly depe
nds on CYP2C19 genotype status. The genotyping test of CYP2C19 may be usefu
l for an optimal prescription of omeprazole.