Proton pump inhibitors (PPIs) are widely used in the treatment of acid-related diseases such as gastroesophageal reflux disease (GERD) and peptic ulcer disease; however, PPIs have relatively short half-lives and do not control nighttime acid secretion or offer rapid symptom relief. Hori et al. describe a new and structurally different potassium-competitive acid blocker, TAK-438 [1-[5-(2-fluorophenyl)-1-(pyridine-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamine monofumarate]. Pharmacokinetic analyses demonstrated that TAK-438 has a short plasma half-life but exhibited a higher accumulation and retention in gastric tissues, potentially explaining the prolonged effect on acid secretion and having the potential to treat nighttime acid secretion. Unlike PPIs, TAK-438 effect on gastric acidity was not affected by pretreatment with cimetidine or stimulation of acid secretion after TAK-438 administration. TAK-438 demonstrated a more potent and longer-lasting antisecretory effect than lansoprazole (a PPI) through high accumulation and slow clearance from gastric tissue. TAK-438 has the potential to exert its full inhibitory effect from the first dose and therefore provide complete control of nighttime acid secretion. These properties of TAK-438 enhance the potential to treat patients with Barrett's esophagus or scleroderma, those refractory to PPIs, or those whose symptoms are insufficiently controlled by PPIs.
See article at J Pharmacol Exp Ther 2011, 337:797–804
- Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics