PBPK-Based Prediction of Obesity-Mediated Changes in Small Molecule Pharmacokinetics

Authors: Le Merdy M, Zhou H, Lukacova V
Conference: AAPS
Keywords: AAPS 2025, gastroplus, MIDD, obesity, PBPK modeling, pharmacokinetics
Software: GastroPlus®

Purpose

  • Obesity is associated with fat accumulation, combined with physiological alterations, (changes in organ sizes, blood flows, and metabolic enzyme activities).
  • These pathophysiological modifications have profound effects on all phases of drugs’ ADME.
  • Dose selection, efficacy prediction, and safety assessment for obese patients are challenging.
  • This applies to drugs designed to support weight loss as well as drugs intended to treat other diseases where obesity is a comorbidity.
  • As part of MIDD, PBPK models are used to assess pharmacokinetic changes in special populations.
  • This study aims to demonstrate the use of PBPK models in predicting obesity-induced changes in the PK of small molecules.

By Maxime Le Merdy, Haiying Zhou,  Viera Lukacova

American Association of Pharmaceutical Scientists (AAPS) PharmSci360, November 9-12, 2018, San Antonio, TX