PBPK Modeling of Acetaminophen in Pediatric Populations: Incorporation of SULT Enzyme Ontogeny to Predict Age-Dependent Metabolism and Systemic Exposure.

ABSTRACT: Sulfotransferase (SULT) enzymes contribute significantly to drug metabolism in pediatric patients. The purpose of this study was to develop a PBPK model for acetaminophen (APAP) in pediatric populations that accounts for the ontogeny of SULT isozymes that play a critical role in APAP metabolism. PBPK modeling and simulation were performed using the Simcyp^® Simulator. The model incorporated the developmental ontogeny of three key hepatic SULT enzymes: SULT1A1, SULT1A3, and SULT2A1 using "best-fit" ontogeny equations for each isozyme as determined by nonlinear regression analysis of enzyme abundance versus age. PBPK model-simulated pharmacokinetic profiles for APAP captured observed clinical data for systemic exposure (Cmax, AUC) in neonates, infants, and children. SULTS accounted

SUBMITTER: Sharma S 

PROVIDER: S-EPMC12300260 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature