Microphysiological Systems As an Emerging in Vitro Approach for the Evaluation of Drug Absorption, Distribution, Metabolism, and Excretion and Toxicity.

Microphysiological systems (MPSs) are emerging in vitro technologies designed to recapitulate human physiology for applications in drug development and safety assessment. Compared with conventional in vitro systems, MPSs may contain multiple types of cells and display dynamic and mechanical features of organ microenvironments. As part of new approach methodologies, MPSs are expected to contribute to reducing reliance on animal testing by providing human-relevant models that align with the principles of replacement, reduction, and refinement. This review discusses the advantages of MPSs over conventional in vitro systems for drug absorption, distribution, metabolism, and excretion and toxicity evaluation. We then systematically examines organ-specific MPS platforms used in absorption, distribution, metabolism, and excretion and toxicity studies. Next, we briefly evaluated the reproducibility of MPSs across different systems. Finally, we provide our perspectives and considerations on employing MPSs in regulatory applications. SIGNIFICANCE STATEMENT: This minireview provides an overview of the current trends in the field of microphysiological systems within the framework of new approach methodologies. This review will give readers insights into key differences between microphysiological systems and other in vitro methods in drug absorption, distribution, metabolism, and excretion, followed by recent advances in several organ chips for drug evaluation.