Physiological Indirect Response Model to Omics-Powered Quantitative Systems Pharmacology Model

• Published in: Journal of pharmaceutical sciences 2024-01, Vol.113 (1), p.11-21
• Main Authors: Uatay, Aydar, Gall, Louis, Irons, Linda, Tewari, Shivendra G, Zhu, Xu Sue, Gibbs, Megan, Kimko, Holly
• Format: Article
• Language: English
• Subjects: Drug Development; Drugs, Investigational; Models, Biological; Models, Theoretical; Network Pharmacology; Pharmacology
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1016/j.xphs.2023.10.032

Over the past several decades, mathematical modeling has been applied to increasingly wider scopes of questions in drug development. Accordingly, the range of modeling tools has also been evolving, as showcased by contributions of Jusko and colleagues: from basic pharmacokinetics/pharmacodynamics (PK/PD) modeling to today's platform-based approach of quantitative systems pharmacology (QSP) modeling. Aimed at understanding the mechanism of action of investigational drugs, QSP models characterize systemic effects by incorporating information about cellular signaling networks, which is often represented by omics data. In this perspective, we share a few examples illustrating approaches for the integration of omics into mechanistic QSP modeling. We briefly overview how the evolution of PK/PD modeling into QSP has been accompanied by an increase in available data and the complexity of mathematical methods that integrate it. We discuss current gaps and challenges of integrating omics data into QSP models and propose several potential areas where integrated QSP and omics modeling may benefit drug development.