Rabeprazole

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Rabeprazole
Rabeprazole.png
Rabeprazole3d.png
Systematic (IUPAC) name
(RS)-2-([4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methylsulfinyl)-1H-benzo[d]imidazole
Clinical data
AHFS/Drugs.com Monograph
MedlinePlus a699060
License data
Pregnancy
category
  • US: B (No risk in non-human studies)
Routes of
administration
Oral
Legal status
Legal status
Pharmacokinetic data
Bioavailability 52%
Metabolism mostly non-enzymatic,
partly hepatic (CYP2C19)
Biological half-life 1 - 1.5 hours
Excretion 90% renal
Identifiers
CAS Number 117976-89-3 YesY
ATC code A02BC04 (WHO)
PubChem CID 5029
IUPHAR/BPS 7290
DrugBank DB01129 YesY
ChemSpider 4853 YesY
UNII 32828355LL YesY
ChEBI CHEBI:8768 YesY
ChEMBL CHEMBL1219 YesY
PDB ligand ID RZX (PDBe, RCSB PDB)
Chemical data
Formula C18H21N3O3S
Molar mass 359.444 g/mol
Chirality Racemic mixture
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Rabeprazole /ˌræ.ˈbɛp.ræ.zɔːl/ is an antiulcer drug in the class of proton pump inhibitors. It was developed by Eisai Co. and is available worldwide under many brand names.

Indications and usage[edit]

Short-term treatment in healing and symptomatic relief of duodenal ulcers and erosive or gastroesophageal reflux disease (GERD); maintaining healing and reducing relapse rates of heartburn symptoms in patients with GERD; treatment of daytime and nighttime heartburn and other symptoms associated with GERD; long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome and in combination with amoxicillin and clarithromycin to eradicate Helicobacter pylori.

  • Gastric ulcer (GU)
  • Peptic ulcer disease (PUD)
  • Maintenance of healing of erosive or ulcerative GERD
  • Healing of erosive and ulcerative GERD
  • Healing of duodenal ulcers.
  • Treatment of symptomatic GERD
  • Treatment of pathological hypersecretory conditions (Zollinger-Ellison syndrome)
  • Helicobacter pylori eradication to reduce risk of duodenal ulcer recurrence

Contraindications[edit]

  • hypersensitivity to rabeprazole, substituted benzimidazoles or any of components of its pharmaceutical forms.
  • lactation: Thomson Lactation Ratings: Infant risk cannot be ruled out.

Restriction of usage[edit]

Bottle of rabeprazole 20 mg tablets.
  • acute liver failure
  • pediatric use in patients under 18 years of age (there are insufficient data about safety and efficiency of rabeprazole in this group of patients)

Side effects[edit]

Rabeprazole adverse reactions/side effects include[citation needed]:

Drug interactions[edit]

Rabeprazole decreases the concentration of ketoconazole in the plasma (in 33%), increases the concentration of digoxin (in 22%), and does not interact with liquid antacids. Rabeprazole is compatible with any medicine metabolized by the CYP450 (theophylline, warfarin, diazepam, phenytoin).

Overdosage[edit]

Studies in mice and rats indicated the symptoms of acute toxicity due to overdose included: hypoactivity, labored respiration, convulsion, diarrhea, tremor, and coma. A study in dogs indicated that a dose of 2000 mg/kg was not lethal.

Synthesis[edit]

Rabeprazole synthesis:[1] patents:[2]

Nitration of 2,3-dimethylpyridine N-oxide affords the nitro derivative. The newly introduced nitro group is then displaced by the alkoxide from 3-methoxypropanol to affords the corresponding ether (3). Treatment with Ac2O results in the Polonovski reaction. Saponification followed by treatment with SOCl2 then chlorinates the primary alcohol (5). Condensation with benzimidazole-2-thiol (6) followed by oxidation of the resulting thioether to the sulfoxide then affords rabeprazole (8).

References[edit]

  1. ^ Tagami, K.; Chiku, S.; Sohda, S. (1993). "Synthesis of 14C-labelled sodium pariprazole (E3810)". Journal of Labelled Compounds and Radiopharmaceuticals. 33 (9): 849. doi:10.1002/jlcr.2580330908. 
  2. ^ S. Souda et al., EP 268956 ; eidem, U.S. Patent 5,045,552 (1988, 1991 both to Eisai).
  • Morii M, Takata H, Fujisaki H, Takeguchi N., The potency of substituted benzimidazoles such as E3810, omeprazole, Ro 18-5364 to inhibit gastric H+, K(+)-ATPase is correlatedwith the rate of acid-activation of the inhibitor, Biochem. Pharmacol. 1990 Feb 15;39(4):661-7.
  • Prakash A, Faulds D., Rabeprazole, Drugs. 1998 Feb;55(2):261-7; discussion 268.

External links[edit]