Case 2000-093
UCLA researchers in the Department of Medicine have discovered a novel method to improve the efficacy of proton pump inhibition.
BACKGROUND:
A vast 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, duodenal ulcers, atrophic gastritis, esophagitis, and the like. Conditions such as GERD and peptic ulcers, in particular, can have severe 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 with repeated use, as well as the adverse side effects associated with the use of larger doses, has lead to the use of proton pump inhibitors (PPIs) and more recently the potassium-competitive acid blockers (P-CABs). These agents reduce potent gastric acid secretion by inhibiting the proton pumps (H+/K+ -ATPase). , However, the use of these agents has been hindered due to the large dose requirements resulting in potential adverse events. Therefore, there is an emerging need to develop a method for the treatment of gastric secretory disorders by utilizing lower doses of medications that inhibit the proton pump.
INNOVATION:
UCLA researchers in the laboratory of Dr. Joseph Pisegna in the Department of Medicine, Division 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 medications that inhibit the proton pump 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.
POTENTIAL APPLICATIONS:
• Therapeutics combining a proton pump inhibitor and pentagastrin
ADVANTAGES:
• Administration of the therapeutics can be done by any route
• Allows for low doses of gastrin, pentagastrin analogues, or derivatives.
• Various proton pump inhibitors can be used, which include, but are not limited to, rabeprazole,
omeprazole, lansoprazole, esomprazole, pantoprazole as well as the newer PCABs vonoprazan
and tegoprazan
DEVELOPMENT-TO-DATE:
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.
RELATED MATERIALS:
Intravenous esomeprazole 40 mg vs. intravenous lansoprazole 30 mg for controlling intragastric acidity in healthy adults. Aliment Pharmacol Ther. (2008)-http://www.ncbi.nlm.nih.gov/pubmed/18162083.