PT  - JOURNAL ARTICLE
AU  - Kim, Dong Kyu
AU  - Lee, Keun-Ho
AU  - Kim, Sung-jun
AU  - Kim, Soo-Jin
AU  - Lee, Song Jin
AU  - Park, Chi Hye
AU  - Kim, Bong-Tae
AU  - Song, Geun-Seog
AU  - Moon, Byoung-Seok
AU  - Ryu, Shin-Young
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 Jun 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 318--327
VI  - 369
IP  - 3
4099  - http://jpet.aspetjournals.org/content/369/3/318.short
4100  - http://jpet.aspetjournals.org/content/369/3/318.full
SO  - J Pharmacol Exp Ther2019 Jun 01; 369
AB  - Tegoprazan, a novel potassium-competitive acid blocker (P-CAB), is a next-generation therapeutics developed for the treatment of 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 were compared with those of esomeprazole, a representative proton pump inhibitor. In vitro enzyme assays were performed using ion-leaky vesicles containing gastric H+/K+-ATPases isolated from pigs. 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, whereas esomeprazole showed weak and irreversible inhibition with an IC50 value of 42.52 μM. In a GERD model, tegoprazan showed dose-dependent efficacy in inhibiting esophageal injury and gastric acid secretion with an ED50 of 2.0 mg/kg, which was 15-fold more potent than that of esomeprazole. In peptic ulcer models, tegoprazan exhibited superior antiulcer activity compared with esomeprazole. The ED50 of tegoprazan in the naproxen-, ethanol-, and water-immersion restraint stress-induced peptic ulcer models were 0.1, 1.4, and 0.1 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% vs. 32.7%, respectively), after 5 days of repeated oral administration. Thus, tegoprazan is a novel P-CAB that shows potent and reversible inhibition of gastric H+/K+-ATPase and may provide stronger efficacy compared with previous proton pump inhibitors.