A Mechanism-Based Multi-Level Population PK/PD Model for Potassium-Competitive Acid Blockers.

ABSTRACT: 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

SUBMITTER: Jung W 

PROVIDER: S-EPMC12823312 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature