PT  - JOURNAL ARTICLE
AU  - Dongkyu Kim
AU  - Keun-ho Lee
AU  - Sung-jun Kim
AU  - Soo-Jin Kim
AU  - Song Jin Lee
AU  - Chi Hye Park
AU  - Bong-Tae Kim
AU  - Geun-Seog Song
AU  - Byoung-Seok Moon
AU  - Shin-Young Ryu
TI  - Effects of tegoprazan, a novel potassium-competitive acid blocker, on rat models of gastric acid-related disease
AID  - 10.1124/jpet.118.254904
DP  - 2019 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - jpet.118.254904
4099  - http://jpet.aspetjournals.org/content/early/2019/03/20/jpet.118.254904.short
4100  - http://jpet.aspetjournals.org/content/early/2019/03/20/jpet.118.254904.full
AB  - Tegoprazan, a novel potassium-competitive acid blocker (P-CAB), is next generation therapeutics in development for acid-related gastrointestinal diseases such as gastroesophageal reflux disease (GERD) and peptic ulcers. In the present study, the in vitro and in vivo pharmacological properties of tegoprazan are compared with those of esomeprazole, a representative proton pump inhibitor. In vitro enzyme assays were performed using the ion-leaky vesicles containing gastric H+/K+-ATPases isolated from porcine. The in vivo efficacies of tegoprazan were evaluated in rat models of GERD and peptic ulcer. Tegoprazan inhibited the activity of porcine H+/K+-ATPase with an IC50 value of 0.53 μM in a reversible manner while esomeprazole showed a weak and irreversible inhibition with an IC50 value of 42.52 μM. In a GERD model, tegoprazan showed a dose-dependent efficacy for the inhibition of esophageal injury and gastric acid secretion with an ED50 of 2.0 mg/kg, which is 15 times more potent than that of esomeprazole. In peptic ulcer models, tegoprazan exhibited superior anti-ulcer activity compared to esomeprazole. The ED50 of tegoprazan in the naproxen-, ethanol-, and water-immersion restraint stress-induced peptic ulcer models were 0.12, 1.41, and 0.11 mg/kg, respectively. In the acetic acid-induced peptic ulcer model, the curative ratio of tegoprazan at 10 mg/kg was higher than that of esomeprazole at 30 mg/kg (44.2% versus 32.7%, respectively), following 5 days repeated oral administration. Hence, tegoprazan is a novel P-CAB that shows potent and reversible inhibition of gastric H+/K+-ATPase and should provide stronger efficacy compared with previous PPIs.