Drug-drug interactions (DDIs) significantly impact drug safety and efficacy, posing a challenge in clinical pharmacology and drug development. Understanding and predicting DDIs, especially those mediated by cytochrome P450 (CYP) enzymes and drug transporters, are crucial for minimizing adverse effects and optimizing therapeutic outcomes. Physiologically Based Pharmacokinetic (PBPK) modeling has emerged as a powerful tool in this arena, offering a mechanistic approach to predict DDIs. Further Novel endogenous biomarkers have been discovered for the early determination of potential DDIs. Concurrently, minimizing off-target toxicities and managing reactive metabolites provide strategic avenues to enhance drug safety.

This collection will cover several crucial aspects of DDIs, integrating advanced modeling techniques, novel biomarkers, and strategies for minimizing off-target toxicities. The goal is to provide a comprehensive collection of studies and reviews that address these challenges from both theoretical and practical perspectives. Key topics to be covered include, but are not limited to:

- Physiologically Based Pharmacokinetic (PBPK) Modeling:
Applications of PBPK modeling in predicting transporter and CYP inhibition- and induction-mediated DDIs, as well as DDIs associated with the use of traditional medicines and biologics. Exploring challenges and progress in incorporating real-world complexities into PBPK models, along with Case studies demonstrating the efficacy of PBPK models in both nonclinical and clinical scenarios.

- Minimizing Off-Target Toxicities:
Strategies for reducing off-target toxicities caused by reactive metabolites; Structural modification of drug candidates to prevent the formation of harmful metabolites; Use of trapping agents to mitigate reactive metabolite formation; Enhancing selectivity of drug candidates to minimize adverse effects

- Endogenous Biomarker-informed Approaches:
Identification and validation of endogenous biomarkers for evaluating transporter- and CYP-mediated DDIs; Application of biomarker-informed approaches in real-time drug behavior analysis; Novel insights into drug-disease interactions, genetic polymorphisms and their impact on DDIs.

- Pharmacological Landscape of Redox-Modulating Therapeutics:
Exploration of redox-modulating agents and their role in influencing oxidative stress pathways; Understanding the interaction mechanisms of redox-modulating therapeutics; Safety and efficacy of integrating redox-modulating agents into therapeutic regimens to mitigate DDI

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Frontiers in Pharmacology

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