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[CLINICAL STUDIES]
Clinical efficacy
The results of open-labeled and double-blind clinical trials
conducted with
PARIET in patients with gastric ulcer, duodenal ulcer, reflux esophagitis and anastomotic ulcer are summarized
in the following table.
| Disease |
Endoscopic healing rate |
| Gastric ulcer |
95.2% ( 401 / 421 ) |
| Duodenal ulcer |
98.1% ( 364 / 371 ) |
| Reflux esophagitis |
90.9% ( 50 / 55 ) |
| Anastomotic ulcer |
83.3% ( 10 / 12 ) |
The overall improvement rate in 2 patients with Zollinger-Ellison syndrome was 100%.
It was demonstrated in clinical pharmacology studies that the increase in gastric pH was greater in the 20 mg group than in the 10 mg group, and the usefulness of
PARIET in the treatment of intractable ulcer has been demonstrated using a dose of 20 mg once daily.
In addition, the clinical usefulness of
PARIET in the treatment of gastric and duodenal ulcers has been demonstrated in
double-blind clinical trials.
[PHARMACOLOGY]
1. Mechanism of action
PARIET transforms to the activated form (sulfenamid form) at parietal cells in acidic conditions, and acts by modification of SH-groups of the proton pump (H+, K+, -ATPase) causing inhibition of enzyme activity and consequents acid secretion suppression. It is believed that the recovery of enzyme activity is mainly due to drug elimination from the active site, or that glutathione may be involved in the elimination of the active drug. The involvement of glutathione in recovery of enzyme activity is also suspected.
2. Action in humans
(1) Inhibition of gastric acid secretion
When
PARIET was administered to healthy adult male volunteers at 10 mg or 20 mg once a day, gastrin-stimulated acid output was significantly decreased compared with the
1st day of administration. The mean percentages of acid output reduction
compared with the day before starting administration on day I and on day 7
were, at 10 mg once a day, 73 % and 80%, and at 20 mg once a day, 88-89% and
99%, respectively.
(2) Increase reaction of intragastric pH
When
PARIET was administered to healthy adult male volunteers at 10 mg or 20 mg once a day, intragastric
pH was significantly increased. The percentage of holding times above pH4
and pH3 in 24 hr on day 4 after treatment with 10 mg was 73 % and 80 %
respectively, and for treatment with 20 mg was 78% and 83%, respectively.
3. Action in animals
(1) Inhibition of H+, K+-ATPase (in vitro)
Sodium rabeprazole strongly inhibits II , K+-ATPase
in preparations made from pig gastric mucosa.
(2) Inhibition of gastric acid secretion
1) Sodium rabeprazole inhibits gastric acid secretion
stimulated by dibutyl cyclic-AMP in isolated rabbit gastric glands (in vitro).
2) Sodium rabeprazole exhibits strong inhibition of gastric acid secretion stimulated by histamine or pentagastrin
in chronic gastric fistula dogs as well as basal gastric acid secretion and
histamine-stimulated gastric acid secretion in rats.
[ PHYSICOCHEMISTRY]
Nonproprietary name: Sodium Rabeprazole(JAN)
Chemical name:
(±)-sodium2-[[4-(3-methoxypropoxy)-3-methylpyridin-2-yl] methylsulfinyl]-1H-benzimidazole
Molecular formula: C18H20N3O3SNa
Molecular weight: 381.43
Structural formula:
Description:
Sodium rabeprazole occurs as a white to pale yellowish white powder. It is odorless. It is very soluble in water and in methanol, freely soluble in dehydrated ethanol and in ethyl acetate, and practically insoluble in ether and in hexane. It shows no optical rotation.
It is hygroscopic.
Melting point: 225°C (with decomposition)
Partition coefficient: about 214 (pH7.0, water: octanol)
[STORAGE AND HANDLING]
Storage:
PARIET should be stored at controlled temperature (1-30°C) and be protected from moisture after unsealing.
Expiration date:
PARIET should be used before the expiration date indicated on the package (It is also recommended that
PARIET be used as soon as possible after unsealing.).
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