Tegoprazan

Tegoprazan is a potassium channel inhibitor with an anti-acid secretion effect. It is metabolized by CYP3A4, a cytochrome enzyme the occurrence of which in the Mexican population, differs from that in some other populations. Since the efficacy and safety studies on tegoprazan have been conducted in Koreans, it is of considerable clinical importance to establish whether differences exist in CYP3A4 metabolism between the two populations.

To evaluate the oral pharmacokinetics of tegoprazan and to compare the pharmacokinetic data with those reported in the literature for Koreans.

The investigation was carried out in a cohort of 20 healthy Mexican volunteers (11 women and 9 men), who were administered a dose of 50 mg after fasting for at least 10 hours. Blood samples were taken at selected time points over 24 hours, and tegoprazan plasma concentrations measured using high-performance liquid chromatography. Pharmacokinetic parameters were compared to those in Koreans reported in the literature.

Tegoprazan is rapidly absorbed from the gastrointestinal tract reaching C_max at ~ 1 hour post dose (t_max) and is removed from the circulation with an average half-life of ~ 4 hours. The pharmacokinetic parameters obtained were similar to those obtained in Koreans including elimination half-life, maximum tegoprazan concentrations, and oral bioavailability.

Since no clinically relevant pharmacokinetic differences were observed in the pharmacokinetics of tegoprazan, a substrate for CYP3A4, between Mexicans and Koreans, it is concluded that the efficacy and safety data for tegoprazan obtained in Koreans will be valid in the Mexican population.

Potassium‐competitive acid blockers (PCABs) are emerging alternatives to proton pump inhibitors for the treatment of acid‐related diseases. However, due to the complex, nonlinear interaction between drug exposure, food intake, and physiological rhythms, optimizing dosing strategies remains challenging. A multi‐leveled population analysis was conducted using published pharmacokinetic and pharmacodynamic data on four representative PCABs: tegoprazan, YH4808, fexuprazan, and vonoprazan. A semi‐mechanistic population PK/PD model was developed to account for food effects, circadian pH rhythms, and pH‐dependent drug absorption. A multi‐level nonlinear mixed‐effects modeling framework was implemented to capture both inter‐drug and inter‐study variability. The model successfully described the time course of plasma concentration and intragastric pH for all four PCABs under various conditions. The model identified differences in pharmacokinetics and pharmacodynamic potency between drugs (with the relative in vitro potency ranked as vonoprazan > fexuprazan > YH4808 > tegoprazan), and simulations demonstrated that both pre‐ and post‐meal administration enhanced pH control in early time period via potentially distinct mechanisms: the pre‐meal effect may arise from temporally separated contributions of food‐ and drug‐induced pH elevation, whereas the post‐meal effect is likely driven by temporally overlapping, additive actions, particularly under low‐dose or non‐steady‐state conditions. Predicted pH profiles and holding times above pH 4 closely matched reported clinical outcomes. The study demonstrates the application of a mechanistic, multi‐level population approach for cross‐drug PK/PD evaluation of PCABs. The findings support drug‐specific dose optimization and highlight the clinical relevance of food–drug interactions. The modeling approach provides a model platform for pharmacotherapy or model‐informed drug development (MIDD).