Potential integration of multiple organs-on-a-chip for comprehensive drug-drug interaction prediction

Predicting drug - drug interactions (DDIs) is essential for safe, effective medication therapy, yet conventional in vitro assays and in silico models are not completely reliable in their assessments. Multi-organ-on-a-chip (MOC) platforms provide a more physiologically relevant approach that may improve in vitro DDI predictions, particularly for complex DDIs.

We outline current DDI workflows, their strengths and limitations, and how single-organ chips can produce quantitative absorption, distribution, metabolism, and excretion (ADME) and toxicity parameters relevant for DDI analysis. We then discuss the need for emerging MOC platforms and the unique advantages that they offer, highlighting case studies that capture more complex DDI scenarios, as well as body-on-a-chip prototypes integrated with mechanistic modeling.

MOC systems are currently poised to complement, not replace, established in vitro and modeling approaches for DDI predictions. Near-term value lies in fit-for-purpose contexts of use, supplying physiologically grounded parameters and mechanistic insight to physiologically based pharmacokinetic (PBPK) modeling. With continued progress in addressing key challenges (e.g. physiological scaling, sorptive materials, microscale analytics, variability, throughput, and standardization), MOCs should mature into reliable tools to assist in DDI prediction, and potentially even qualified assays as part of regulatory DDI risk assessment frameworks.