Mechanistic Insights into Cytokine Antagonist-Drug Interactions: A Physiologically Based Pharmacokinetic Modelling Approach with Tocilizumab as a Case Study.

ABSTRACT: Background: Understanding interactions between cytokine antagonists and drugs is essential for effective medication management in inflammatory conditions. Recent regulatory authority guidelines emphasise a systematic, risk-based approach to evaluating these interactions, underscoring the need for mechanistic insight. Proinflammatory cytokines, such as interleukin-6 (IL-6), modulate cytochrome P450 (CYP) enzymes, reducing the metabolism of CYP substrates. Cytokine antagonists (such as IL-6 receptor antagonists) can counteract this effect, restoring CYP activity and increasing drug clearance. However, quantitative prediction of cytokine-mediated drug interactions remains challenging, as existing models often lack the mechanistic detail needed to capture the dynamic relationship betwee

SUBMITTER: Pan X 

PROVIDER: S-EPMC12297905 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature