Proton pump inhibitors development

Esomeprazole in the Framework of Proton-Pump Inhibitor Development... 

Gastrointestinal Nexium the first proton pump inhibitor developed as an isomer AstraZeneca Leading... 

Low-dose maintenance therapy with a proton pump inhibitor or histamine2-receptor antagonist is only indicated for patients who fail HP eradication, have HP-negative ulcers, or develop severe complications related to their ulcer disease. 

AstraZeneca launched omeprazole in 1988. It is a safe and effective drug for acid reflux, functioning as a proton pump inhibitor. However, the patent has expired and AstraZeneca has to compete against generics. The company developed the active isomer and called it esomeprazole. It was approved by the Mutual Recognition process in Europe in July 2000, and by the US Food and Drug Administration in February 2001. The chemical formulas for omeprazole and esomeprazole are shown below. 

Proton pump inhibitors (PPIs), such as omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole, are commonly prescribed to treat symptoms of heartburn, acid reflux, chest pain, dyspepsia, and chronic cough. PPIs inhibit the transfer of protons into the stomach lumen. Pharmacological acid suppression is thus used to treat gastroesophageal reflux disease (GERD) and esophagitis, peptic ulcers, and Helicobacter pylori infection as well as to prevent ulcer development with concurrent nonsteroidal anti-inflammatory drug use. 

A third basic option available in the case of some therapeutic categories is to develop an over-the-counter version of a product subject to patent expiration. The strategy has been employed for example for anti-inflammatory pain relievers such as Motrin and Naprosyn, anti-ulcer therapies such as the H2 blockers Tagamet and Zantac, proton pump inhibitors such as Prilosec, and in several other therapeutic categories. However, a shift to OTC status requires approval by the FDA that the drug is safe for self-medication (Juhl 2000 McCarran 1991 Schweitzer 1997). A company will normally need to submit new clinical trial evidence to that effect. If approved by the FDA, the company receives a three-year exclusivity period for its OTC product in recognition for the new clinical trial work. 

Revaprazan is a reversible proton pump inhibitor. It is currently in Phase 111 clinical development as a treatment for peptic ulcer (Figure 8.70). 

Asymptomatic peptic ulceration develops in 10-20% of people taking frequent NSAIDs, and ulcer-related complications (bleeding, perforation) develop in 1-2% of persons per year. Proton pump inhibitors taken once daily are effective in reducing the incidence of ulcers and ulcer complications in patients taking aspirin or other NSAIDs. 

El-Sherif et al. [79] developed and validated a reversed-phase HPLC method for the quantitative determination of omeprazole and two other proton pump inhibitors in the presence of their acid-induced degradation products. The drugs were monitored at 280 nm using Nova-Pak Ci8 column and mobile phase consisting of 0.05 M potassium dihydrogen phosphate-methanol-acetonitrile (5 3 2). Linearity range for omeprazole was 2-36 fig/ml. The recovery of omeprazole was 100.50 0.8%, and the minimum detection was 0.54 /zg/ml. The method was applied to the determination of pure, laboratory prepared mixtures, and pharmaceutical dosage forms. The results were compared with the official USP method for omeprazole. 

Pantoprazole sodium, a substituted benzimidazole derivative, is an irreversible proton pump inhibitor, and was developed for the treatment of acid-related gastrointestinal disorders. As with other drugs of its class (e. g. omeprazol or lansoprazole), pantoprazole reduces gastric acid secretion through inhibition of the portion on the gastric parietal cell. In combination with other drugs, pantoprazole can be used for the initial treatment of H. Pylori infection [1],... 

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