LAUSR

AIM The new modified-release formulation of tegoprazan, a novel potassium-competitive acid blocker, is expected to improve the management of acid-related disease, including nocturnal acid breakthrough, by prolonging the duration of acid suppression. This study aimed to explore the pharmacokinetics (PK) and pharmacodynamics (PD) of various combinatorial tegoprazan with immediate-release (IR) and delayed-release (DR) formulations. METHODS A three-cohort, open-label, randomized, single-dose, three-treatment, six-sequence, three-period crossover study was conducted. Various combinations of tegoprazan IR and DR formulations (50, 75, or 100 mg) were administered orally once per period. The 24-hour intragastric pH was monitored before and after each administration. PK blood samples were collected for up to 48-hour. PK and PD were compared among treatments. RESULTS Eighteen healthy Korean subjects completed the study. All treatment groups showed intragastric pH above 4 approximately 1-hour following tegoprazan administration. Among the various combinations, the IR and DR combination at a 1:1 ratio induced greater gastric acid suppression (%Time pH≥4) than IR alone in each dose groups, both for 24-hour (50 mg; 59 % vs. 52%, P=0.2188, 95% confidence interval (CI) -6.92-22.27, 100 mg; 85% vs. 70%, P<0.05, 95% CI 8.92-22.19) and at night (50 mg; 27% vs. 16%, P=0.1563, 95% CI -11.79-37.71, 100 mg; 77% vs 49%, P<0.05, 95% CI 16.14-42.98), with similar systemic exposure. CONCLUSION The combinatorial tegoprazan in the IR and DR 1:1 ratio formulation was found to induce stronger gastric acid suppression throughout the day and at night, compared to the conventional IR formulation.