People may have differences in their capacity to metabolize rabeprazole to an inactive metabolite. This may be mediated through genetic differences in the gene that encodes for the metabolic enzyme CYP2C19. For example, people that are poor CYP2C19 metabolizers (i.e. their version of CYP2C19 is less effective than average) will have trouble metabolizing rabeprazole, allowing the active rabeprazole to stay in the body, where it can exert its effect, longer than intended. Conversely, extensive CYP2C19 metabolizers (i.e. the average metabolic capacity of CYP2C19) will extensively metabolize rabeprazole, as expected. The poor metabolizing CYP2C19 phenotype is found in roughly 3–5% of Caucasian people, and in 17–20% of people of Asian ancestry. In a study on men of Japanese ancestry, this has translated to an average increase of total drug exposure by 50–60% compared to men in the United States.However, rabeprazoles metabolism is primarily non-enzymatic (it is often inactivated chemically, without the participation of the bodys natural drug metabolizing enzymes). Therefore, while a persons CYP2C19 phenotype will affect rabeprazoles metabolism, it is not expected to dramatically affect the efficacy of the medication. Chemistry
Rabeprazole is classified as a substituted benzimidazole, like omeprazole, lansoprazole, and pantoprazole. Rabeprazole possess properties of both acids and bases, making it an amphotere. The acid dissociation constant (pKa) of the pyridine nitrogen is about equal to 5. Synthesis
The above synthesis pathway begins with 2,3-dimethypyridine N-oxide (1).
Rabeprazole, sold under the brand name Aciphex, among others, is a medication that decreases stomach acid. It is used to treat peptic ulcer disease, gastroesophageal reflux disease, and excess stomach acid production such as in Zollinger–Ellison syndrome. It may also be used in combination with other medications to treat Helicobacter pylori. Effectiveness is similar to other proton pump inhibitors (PPIs). It is taken by mouth.Common side effects include constipation, feeling weak, and throat inflammation. Serious side effects may include osteoporosis, low blood magnesium, Clostridium difficile infection, and pneumonia. Use in pregnancy and breastfeeding is of unclear safety. It works by blocking H+/K+-ATPase in the parietal cells of the stomach.Rabeprazole was patented in 1986, and approved for medical use in 1997. It is available as a generic medication. In 2017, it was the 279th most commonly prescribed medication in the United States, with more than one million prescriptions. Medical uses
Rabeprazole, like other proton pump inhibitors such as omeprazole, is used for the purposes of gastric acid suppression. This effect is beneficial for the treatment and prevention of conditions in which gastric acid directly worsens symptoms, such as duodenal and gastric ulcers. In the setting of gastroesophageal reflux disease (GERD), whose pathophysiology is characterized by prolonged exposure to gastric acid in the esophagus (often due to changes in stomach and/or esophagus anatomy, such as those induced by abdominal obesity), acid suppression can provide symptomatic relief.