Mass balance and metabolite profiles in humans of tegoprazan, a novel potassium-competitive acid blocker, using 14C-radiolabelled techniques.

Abstract

Background: Tegoprazan (LXI-15028), a novel potassium-competitive acid blocker, has shown great efficacy in treating acid-related disorders. However, its metabolic and excretion characteristics are not fully understood.

Research design and methods: A single oral dose of 50 mg/150 μCi [¹⁴C]tegoprazan was administered to six healthy subjects. Blood, urine and fecal samples were collected and measured for total radioactivity (TRA), tegoprazan and metabolites. Its safety was also assessed.

Results: The maximum concentrations (C_max) of tegoprazan and TRA in plasma were 634 ng/mL and 990 ng eq./mL, respectively, at 0.5 h post dose. Tegoprazan and its N-demethylation metabolite (M1) were the major drug-related compounds in plasma, accounting for 34.84% and 40.10% of TRA, respectively. The half-life (t_1/2) of TRA (8.72 h) was longer than that of tegoprazan (4.33 h) in plasma, indicating slower metabolite elimination. Tegoprazan was excreted through both the urine (50.51 ± 3.35%) and feces (47.26 ± 3.06%). The main metabolic pathways of tegoprazan are demethylation, oxidation, glucuronidation and sulfation. There were no serious adverse events observed in this study.

Conclusions: Tegoprazan is widely metabolized and excreted completely in humans. Tegoprazan and M1 were the primary compounds present in the circulation.

Clinical trial registration: www.clinicaltrials.gov identifier is NCT05883306.