Comparison of the effect on intragastric pH of a single dose of omeprazole or rabeprazole: which is suitable for on-demand therapy?
OBJECTIVE
An ideal medication for heartburn should have the rapid onset of action needed for on-demand treatment. However, assessment of the onset of action of proton pump inhibitors has been largely subjective. We compared the inhibitory effect on gastric acid secretion of a single oral dose of omeprazole with that of rabeprazole.


METHODS
Fourteen Helicobacter pylori-negative men participated in this randomized, double-masked, two-way cross-over study. Intragastric pH was monitored continuously for 6 h after a single, randomly assigned 20 mg oral dose of either omeprazole or rabeprazole. After a 7-day washout period, the other drug was administered. Each patient's S-mephenytoin 4'-hydroxylase (CYP2C19) genotype was determined by polymerase chain reaction-restriction fragment length polymorphism.


RESULTS
Intragastric pH and pH holding time did not differ between treatments when the data were analyzed for the whole group without stratifying for CYP2C19 status. In CYP2C19 homozygous and heterozygous extensive metabolizers (10 subjects), rabeprazole maintained the intragastric at pH > 3 and> 4 for longer than omeprazole during both the 5 and 6 h study periods, and the average pH during the 6 h study period was higher with rabeprazole than with omeprazole. In these extensive metabolizers, rabeprazole maintained the pH > 2,> 3,> 3.5 and> 4 for longer during the 6 h study period than did omeprazole.


CONCLUSIONS
In H. pylori-negative men who are CYP2C19 homozygous or heterozygous extensive metabolizers, the intragastric pH after a single dose of 20 mg rabeprazole is higher during first 5-6 h than that after a single dose of 20 mg omeprazole.
Inamori
Masahiko
M
The Third Department of Internal Medicine, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. inamorim@med.yokohama-cu.ac.jp
Togawa
Jun-ichi
J
Takahashi
Kirokazu
K
Yoneda
Masato
M
Fujisawa
Nobutaka
N
Iwasaki
Tomoyuki
T
Ozawa
Yutaka
Y
Kikuchi
Taisuke
T
Muramatsu
Kenichi
K
Chiguchi
Gaku
G
Matsumoto
Shuhei
S
Kawamura
Harunobu
H
Abe
Yasunobu
Y
Kirikoshi
Hiroyuki
H
Kobayashi
Noritoshi
N
Sakaguchi
Takashi
T
Takamura
Tomoo
T
Nakajima
Atsushi
A
Ueno
Norio
N
Sekihara
Hisahiko
H
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000328:Adult; D000897:Anti-Ulcer Agents / Q000008:administration & dosage*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D001562:Benzimidazoles / Q000008:administration & dosage*; D065731:Cytochrome P-450 CYP2C19; D004311:Double-Blind Method; D005745:Gastric Acidity Determination; D005753:Gastric Mucosa / Q000378:metabolism*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics; D009853:Omeprazole / Q000008:administration & dosage*; D064750:Rabeprazole; D013270:Stomach / Q000187:drug effects*
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D064750:Rabeprazole; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole