Background
A wide number of pathological conditions are characterized by over-secretion of gastric acid, such as Zollinger/Ellison syndrome (ZES), gastroesophageal reflux disease (GERD), peptic ulcer disease, duodenalulcers, atrophic gastritis, esophagitis, and the like. Conditions such as ZES and peptic ulcers, in particular, can have serious complications and represent some of the most prevalent diseases in industrialized nations. Current therapies require high and repeated doses of acid output (AO) inhibiting agents, such as histamine H2-antagonists, to reduce intragastric acidity. However, the inconsistent and diminishing effect of the antagonist, as well as the adverse side effects associated with the use of larger doses has lead to the use of proton pump inhibitors (PPI). PPIs reduce potent gastric acid secretion by inhibiting H+/K+ -ATPase, an enzyme that plays a crucial role in preventing the aggravation of peptic ulcers by reducing pH levels in the stomach. However, the use of PPIs has been hindered due to the large dose requirements. Therefore, there is an emerging need to develop a method for the treatment of GI inflammatory diseases that require lower dosages of PPIs.
Innovation
UCLA researchers in the laboratory of Dr. Joseph Pisegna in the department of Gastroenterology have developed a novel method to optimize the treatment of pathological conditions characterized by excess gastric acid secretion. The method utilizes pentagastrin, an analog of gastrin that indirectly stimulates the proton pump, in conjunction with PPIs to increase the efficacy of gastric acid secretion. The present invention provides an improved method for achieving higher levels of acid reduction at lower dosages unattainable by the use of PPIs alone.
Applications
- Therapeutic combining a PPI and pentagastrin.
Advantages
- Administration of the gastrin, pentagastrin analogues, or derivatives and the PPI can be by any route convenient for the application of these agents.
- Low gastrin, pentagastrin analogues, or derivatives dosages, which range from about 0.1 mg/kg/hr to about 10 mg/kg/hr.
- Various proton pump inhibitors can be used which include, but are not limited to rabeprazole, omeprazole, lansoprazole, and pantoprazole.
State Of Development
Clinical studies demonstrate that a single dose of intravenous (i.v.) pantoprazole rapidly and effectively reduces gastric acid secretion in a dose-dependent manner to normal levels in subjects exposed to continuous i.v. pentagastrin infusion. A single dose of i.v. pantoprazole, either 80 mg or 120 mg, reduced AO levels as quickly and more potently than did i.v. famotidine (histamine H2-antagonist) 20 mg, and had a duration of action approximating 24 h. Furthermore, these data predict that gastric acid secretion can by safely and effectively controlled by i.v. pantoprazole at a dose of 80 mg in patients with gastric acid hypersecretory disorders such as ZES, and that i.v. pantoprazole is preferable to i.v. famotidine.