Assessing DDI risks in drug discovery and development: approaches, challenges, and trends

Moving beyond a purely defensive stance, we must strategically manage the dual nature of drug-drug interactions across the entire drug lifecycle. This capability is built on a proactive framework that seamlessly integrates multi-faceted data (computational, in vitro, and clinical) to continuously forecast DDI risks and opportunities. The ultimate endpoint of DDI assessment is its clinical impact, quantified through PBPK-DDI-pharmacodynamics (PD) and PBPK-DDI-Toxicity (Tox) models. Rigorous benchmarking of all these predictive methods remains essential to close the translational gap, enhance R&D efficiency, and advance more viable drug candidates.