Anti-ulcer drug
Rabeprazole sodium is a anti-ulcer disease drug belonging to proton pump inhibitor and is the sodium salt form of Rabeprazole. The Japanese company Eisai had successfully developed it for the first time with the trade name being “Bolite”. The function of the proton pump inhibitors is reducing the gastric acid secretion so that the lesion site can be stable in order to achieving the effect of curing gastric and duodenal ulcers and stomach-esophageal reflux disease. Clinically it is majorly used for the treatment of acid-related diseases such as stomach and duodenal ulcers, peptic ulcer, gastroesophageal reflux disease and zollinger-ellison syndrome.
Rabeprazole is a kind of benzimidazole-substituted compounds. It inhibits the secretion of gastric acid through forming bond with the cytoplasmic proton pump in the gastric cavity wall. This product can specifically inhibit the effect of the adenosine triphosphatase that is the key enzyme during the production of stomach acid. It has inhibitory effect on both basal gastric acid and the gastric acid secretion caused by the stimulation.
Rabeprazole is white-yellowish-white powder with no odor and a molecular weight being 381.43. This product is highly soluble in water or methanol, also soluble in ethanol or ethyl acetate but almost insoluble in ether or ethane. This product does not exhibit optical activity, has hygroscopic effect. Its melting point is 225 ℃ and its partition coefficient at water/octane system of pH 7.0 is about 214. This product is light yellow film-coated tablets (enteric-coated tablets).
Adverse reactions and precautions: gastric cancer should be excluded after use of the drug. Adverse reactions include allergic reactions, palpitations, constipation, diarrhea, headache, edema, leukopenia, AST, ALT, total bilirubin and proteinuria. The combination of Rabeprazole sodium and digoxin can cause increased digoxin concentration. It can’t be taken simultaneously with antacids. Patients of history of drug allergy, cirrhosis, the elderly, pregnant and lactating women, children should take with caution.
The above information is edited by the chemicalbook of Dai Xiongfeng.
Description
Rebeprazole sodium was launched as Pariet in Japan, its first market, for the treatment of peptic ulcers including gastric and duodenal ulcers. From 4-chloro- 2,3-dimethylpyridine N-oxide, a six step synthesis allows access to the basic skeleton after successive condensations. Rabeprazole, a structural analog of Omeprazole, the first compound to have been marketed in this class up to now, is reported to be a more potent inhibitor of gastric H+/K+-adenosine triphosphate (ATPase) ; a common mechanism of action of this chemical class involves the conversion at low pH to a reactive sulphonamide that itself binds to cysteine residues located on the enzyme. Moreover, rabeprazole showed an antibacterial activity against Helicobacter Pylori, with a MIC90 of 1.56 μg/ml.
Rebeprazole sodium has a faster onset of action compared with omeprazole, but a shorter duration of action, being extensively and rapidly metabolized in several animal species. In clinical studies in patients with gastric ulcers, 10 and 20 mg rabeprazole sodium once-daily significantly inhibited basal and stimulated acid output. Rabeprazole is awaiting registration in the US for treatment of gastrooesophageal reflux disease (GORD) and other pathologic hypersecretory conditions including Zollinger-Ellison syndrome.
Description
Rabeprazole is a proton pump inhibitor that selectively and irreversibly inhibits the gastric H
+/K
+ ATPase (IC
50 = 72 nM). It can be activated more rapidly and over a greater pH range than other proton pump inhibitors such as omeprazole , lansoprazole , and pantoprazole . Rabeprazole (30 mg/kg) inhibits gastric acid secretion in pylorus-ligated rats and a rat model of gastric fistula. It also inhibits the growth of several strains of
H. pylori in vitro (MIC
50s = 1.57-3.13 μg/mL). Formulations containing rabeprazole have been used in the treatment of ulcers, pathological hypersecretory conditions, and gastroesophageal reflux disease (GERD).
Chemical Properties
Rebeprazole sodium is White Crystalline Solid
Uses
Rebeprazole sodium is a partially reversible gastric proton pump inhibitor. It belongs to a national second-class drug that can be used for the treatment of gastric ulcers. It can treat peptic ulcer, gastroesophageal reflux disease, zollinger-ellison syndrome and other diseases. This compound has the effects of anthelminthic, antiseptic, and expectorant. As an antibacterial and antifungal agent, it is effective against gram-positive and gram-negative bacteria, yeast and fungi.
Definition
ChEBI: Rabeprazole sodium is an organic sodium salt. It contains a rabeprazole(1-).
brand name
Aciphex (Eisai Medical Research)
.
General Description
Rabeprazole sodium, 2[[[4-(3-methoxypropoxy)-3-methyl-2-pyridinyl]methyl]sulfinyl]-1H-benzimidazole sodium salt (Aciphex), is a white toslightly yellowish white solid. It is very soluble in water andmethanol, freely soluble in ethanol, chloroform, and ethyl acetate,and insoluble in ether and hexane. Rabeprazole is aweak base (pyridine N, pKa 4.53) and a weak acid (benzimidazoleN-H, pKa 0.62), faciliting sodium salt formation.
Rabeprazole sodium is formulated as enteric-coated,delayed-release tablets to allow the drug to pass throughthe stomach relatively intact. After oral administration of20-mg peak plasma concentrations (C
max) occur over arange of 2 to 5 hours (T
max). Absolute bioavailability for a20-mg oral tablet of rabeprazole (vs. IV administration) isapproximately 52%. The plasma half-life ofrabeprazole ranges from 1 to 2 hours. The effects of foodon the absorption of rabeprazole have not been evaluated.Rabeprazole is 96% bound to human plasma proteins.Rabeprazole is extensively metabolized in the liver. Thethioether and sulfone are the primary metabolites measuredin human plasma resulting from CYP3A oxidation.Additionally, desmethyl rabeprazole is formed via the actionof CYP2C19. Approximately 90% of the drug is eliminatedin the urine, primarily as thioether carboxylic acidand its glucuronide and mercapturic acid metabolites. Theremainder of the dose is recovered in the feces. No unchangedrabeprazole is excreted in the urine or feces.
Biochem/physiol Actions
Rabeprazole sodium is gastric proton pump inhibitor. It suppresses the production of acid in the stomach by inhibiting the gastric H+/K+ATPase (hydrogen-potassium adenosine triphosphatase) at the secretory surface of the gastric parietal cell. Rabeprazole sodium has been used clinically to treat acid-reflux disorders (GERD), peptic ulcer disease, H. pylori eradication, and prevent gastroinetestinal bleeds associated with NSAID use.
Clinical Use
Gastric acid suppression
Drug interactions
Potentially hazardous interactions with other drugs
Antifungals: absorption of itraconazole and
ketoconazole reduced; avoid with posaconazole.
Antivirals: concentration of atazanavir and rilpivirine
reduced - avoid; concentration of raltegravir and
saquinavir possibly increased - avoid.
Clopidogrel: possibly reduced antiplatelet effect.
Cytotoxics: possibly reduced excretion of
methotrexate; avoid with dasatinib, erlotinib and
vandetanib; possibly reduced lapatinib absorption;
possibly reduced absorption of pazopanib.
Ulipristal: reduced contraceptive effect, avoid with
high dose ulipristal.
Metabolism
Rabeprazole is mainly metabolised via nonenzymatic
reduction and, to a lesser extent, via the cytochrome P450
isoenzymes CYP2C19 and CYP3A4. Metabolites are
excreted principally in the urine (about 90%) with the
remainder in the faeces.
