Recent advances and expanding applications of organoid models in unveiling drug ADME profiles

Organoids are three-dimensional (3D) in vitro models generated from stem or progenitor cells that closely replicate the structural and functional complexity of human organs. These systems are emerging as powerful tools in pharmacokinetic research, addressing key limitations of traditional models such as two-dimensional (2D) cell cultures and animal experiments, which are often constrained by physiological mismatch and species-specific differences. This review summarizes recent advances in the development of organoid models, with a focus on hepatic and intestinal systems, and highlights their application in studying drug absorption, distribution, metabolism, and excretion (ADME). We discuss how organoids improve predictions of oral bioavailability, facilitate assessment of drug-drug interactions (DDI), and help interpret interindividual pharmacokinetic variability. Current challenges including incomplete functional maturation, lack of standardization, and limited vascularization are also considered. Finally, we explore future directions involving the integration of organoids with advanced microphysiological systems (such as organ-on-a-chip (OoC)) and artificial intelligence (AI). With ongoing refinement, organoid-based approaches are expected to significantly improve the efficiency of drug development and the accuracy of clinical translation, paving the way for advances in precision pharmacology and personalized medicine.