2025 AIChE Annual Meeting

(689d) A Systems Pharmacology Framework for Whole-Body Drug Metabolism and Biomarker Analysis

Authors

Faiz Khan Mohammad - Presenter, Indian Institute of Technology Madras
Ines Thiele, University of Luxembourg
A comprehensive model that integrates drug pharmacokinetics and its effects on metabolism is essential for drug efficacy assessment in quantitative systems pharmacology. However, existing WBM models lack a systematic framework to capture dynamic interactions between physiologically based pharmacokinetic (PBPK) processes and metabolic networks. To address this limitation, we present a novel modelling framework that integrates PBPK models with steady-state WBM models through progressive time steps, enabling continuous metabolic feedback. This integration is achieved by leveraging whole body metabolic networks as interfaces, ensuring the simultaneous representation of drug metabolism, biomarker fluctuations, and endogenous metabolic pathways across physiological compartments. Our framework captures the metabolism of both exogenous drugs and endogenous biomarker metabolites, providing mechanistic insights into metabolic perturbations and drug-induced changes in biochemical pathways. This approach enhances predictive capabilities for drug efficacy, toxicity risk assessment, and disease-related metabolic adaptations. By bridging PBPK and WBM models, our framework advances quantitative systems pharmacology, offering a powerful tool for precision medicine and improving our understanding of drug behaviour at the whole-body level.