Nitration of 2,3-dimethylpyridine N-oxide affords the nitro derivative (the addition of NO2) (2) The newly introduced nitro group is then displaced by the alkoxide from 3-methoxypropanol to yield the corresponding ether (3). Treatment with acetic anhydride results in the Polonovski reaction. Saponification followed by treatment with thionyl chloride then chlorinates the primary alcohol (5). Reaction with benzimidazole-2-thiol (6) followed by oxidation of the resulting thioether to the sulfoxide yields the final product: rabeprazole (8). Physiochemical properties
Rabeprazole is characterized as a white to yellowish-white solid in its pure form. It is soluble in a number of solvents. Rabeprazole is very soluble in water and methanol, freely soluble in ethanol, chloroform, and ethyl acetate, and is insoluble in ether and n-hexane. It is unstable under humid conditions. History
Rabeprazole was first marketed in Europe in 1998. In 1999, one year later, rabeprazole was approved for use in the United States. Development
Developed by Eisai Medical Research by the research names E3810 and LY307640, the pre-investigational new drug application was submitted on October 28, 1998. The final investigational new drug application was submitted August 6, 1999. On August 19, 1999, rabeprazole was approved in the US for multiple gastrointestinal indications. The approval for the treatment of symptomatic gastroesophageal reflux disease was on February 12, 2002. Society and culture
Legal status
Rabeprazole is approved in the United States and the United Kingdom for prescription use only. Rabeprazole was approved in India in December 2001. It was approved in Japan in 1997, and in all European Union member countries since.
Avoiding rabeprazole during breastfeeding confers to lowest possible risk. Geriatrics
Advanced age does not appear to clinically impact rabeprazoles metabolism. However, elevations in the maximum plasma concentration and the total drug exposure (area under the curve, AUC) have occurred. Japanese ancestry
In a study on rabeprazoles pharmacokinetics, the AUC was elevated by approximately 50–60% in men of Japanese ancestry compared to men in the United States. See the pharmacogenetics section below for a pharmacogenetic explanation of these findings. Kidney or liver problems
In people that have kidney or liver problems, these problems do not appear to affect rabeprazoles metabolism in a clinically meaningful way. This includes individuals on dialysis for kidney problems. Severe liver problems like cirrhosis of the liver do affect rabeprazoles elimination half-life, but not to a degree of dangerous accumulation. In a review of patients taking rabeprazole while having end-stage kidney disease and mild-to-moderate severity, chronic compensated cirrhosis of the liver, the alteration in rabeprazoles metabolism was not clinically meaningful. Contraindications
Rabeprazole is contraindicated in the following populations and situations:
people with a known hypersensitivity to rabeprazole, substituted benzimidazoles (which are chemically similar to rabeprazole, like omeprazole), or any other component of the capsule formulation (e.g. certain dyes)
concurrent use of rilpivirine, a medication used to treat HIV infection

Hypersensitivity
Syndrome
An allergy to a PPI like rabeprazole may take the form of type I hypersensitivity or delayed hypersensitivity reactions. A selective (pattern C—see below for a discussion of cross-reactivity patterns) type I hypersensitivity reaction to rabeprazole resulting in anaphylaxis has been reported, as well as several whole group hypersentivities.