Evaluation of the PK/PD Changes on MASLD-Related Population-An Example From Simultaneous Acetaminophen Parent-Metabolite PBPK/PD Modeling.

ABSTRACT: Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) may exhibit altered pharmacokinetics (PK) and pharmacodynamics (PD) of drugs compared with healthy populations. However, no physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model has been specifically developed for MASLD. Acetaminophen (APAP), a widely used analgesic, was selected to develop a PBPK/PD model predicting PK/PD changes of APAP and its metabolites in MASLD-related populations. Based on a comprehensive review of published APAP PK studies and examination of existing PBPK models, a simultaneous parent-metabolite PBPK model for APAP was developed and optimized in healthy people. The model simulated the dynamics of APAP and its five major metabolites: APAP-glucuronide (APAP-glu), APAP-sulfa

SUBMITTER: Zhao S 

PROVIDER: S-EPMC12823458 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature