Evaluation of Obesity‐Related Physiological Changes on Pantoprazole Clearance in Children Using a Population Pharmacokinetic Approach

• DOI: 10.1002/jcph.6122
• Publication Date: 2024-08-27T14:15:21Z
• Authors: Tyler C. Dunlap; Daniel Gonzalez; Kathryn E. Kyler; Victória Etges He...; Veronica Williams; Chance S. Friesen; Nathan Artz; Sherwin Chan; Valentina Shakhno...
• Keywords: Pantoprazole; Pharmacodynamics

Pediatric obesity is a growing health concern, affecting millions of children worldwide. While pharmacokinetic (PK) changes in numerous commonly prescribed medications have been linked to obesity, the physiological mechanisms driving these alterations and their implications for drug dosing remain poorly understood. The objective this study was evaluate previously reported observations reduced pantoprazole clearance (CL) with investigate obesity-related characteristics liver physiology as explanatory causes observations, clinical relevance on dosing. A prospective, comparative PK study, enrolling participants 6-21 years age, without conducted association between CL. nonlinear mixed-effects modeling approach used identify sources interindividual variability PK. Monte Carlo simulations were performed assess exposure exposure. population consisted 39 pediatric participants: 31% 69% obesity. two-compartment model covariate effects total body weight (TBW), CYP2C19 metabolizer phenotype, status adequately described data. After accounting differences due TBW associated an estimated 18% reduction CL (comparable loss function allele). Further research warranted increased size