Acid-suppressive effects of rabeprazole: comparing 10mg and 20mg twice daily in Japanese Helicobacter pylori-negative and -positive CYP2C19 extensive metabolisers.
BACKGROUND
Rabeprazole 10mg b.i.d. is often administered as therapy for eradication of Helicobacter pylori (H. pylori) and is also proposed as therapy for refractory gastro-oesophageal reflux disease. However, there has not been a comprehensive assessment of its acid-suppressive effects.


OBJECTIVE
To compare the acid-suppressive effects of rabeprazole 10mg b.i.d. with 20mg b.i.d. considering H. pylori status.


METHODS
Thirteen H. pylori-negative and eleven H. pylori-positive Japanese CYP2C19 extensive metabolisers (<35 years).


METHODS
Intragastric pH was measured for 24h three times in a randomised manner; on day 7 of the repeated administration of rabeprazole 10mg b.i.d. or 20mg b.i.d., or a placebo.


RESULTS
In median intragastric pH value and percent time of pH>3.0, >4.0, >5.0, >6.0, and >7.0 for 24h, no significant differences were observed between the two doses in either H. pylori-negative or H. pylori-positive subjects. At either dose, these parameters were significantly higher in H. pylori-positive subjects than in H. pylori-negative subjects. Nocturnal acid breakthrough occurred in seven and two of the thirteen H. pylori-negative subjects and one and two of the eleven H. pylori-positive subjects at each dose, respectively.


CONCLUSIONS
The effects of rabeprazole 10mg b.i.d. were equal to those of 20mg b.i.d. in H. pylori-positive subjects; whereas in H. pylori-negative subjects, 20mg b.i.d. was superior for prevention of nocturnal acid breakthrough.
Shimatani
T
T
Department of General Medicine, Hiroshima University Hospital, 1-2-3 Kasumi, Hiroshima 734-8551, Japan. tshima@hiroshima-u.ac.jp
Moriwaki
M
M
Xu
J
J
Tazuma
S
S
Inoue
M
M
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000008:administration & dosage*; D000328:Adult; D000897:Anti-Ulcer Agents / Q000008:administration & dosage*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D018592:Cross-Over Studies; D065731:Cytochrome P-450 CYP2C19; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005745:Gastric Acidity Determination; D005764:Gastroesophageal Reflux / Q000188:drug therapy* / Q000382:microbiology; D005838:Genotype; D016481:Helicobacter Infections / Q000188:drug therapy / Q000235:genetics*; D016480:Helicobacter pylori; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007564:Japan; D006899:Mixed Function Oxygenases / Q000235:genetics*; D020116:Pepsinogen A / Q000097:blood; D020115:Pepsinogen C / Q000097:blood; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors; D064750:Rabeprazole; D013270:Stomach / Q000737:chemistry
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D064750:Rabeprazole; D020115:Pepsinogen C; D020116:Pepsinogen A; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D006180:Proton-Translocating ATPases