药物代谢创新模型:基因编辑大鼠和小肠3D类器官

Drug metabolism and pharmacokinetics (DMPK) are the science to study the process of drug absorption, distribution, metabolism and excretion. It is very important to evaluate the characteristics of DMPK for the early development of drugs and the later clinical precision medication. The innovative construction of DMPK models promotes the development and improvement of drug evaluation system. Based on our research results, this review summarized the latest progress and application of innovative DMPK models, focusing on the following two aspects: (1) CRISPR/Cas9 gene editing rat models, including Cyp2e1^-/-, Cyp3a1/2^-/-, Cyp2j3/10^-/-, Cyp1a2^-/-, Mdr1a/1b^-/-, Slco1b2^-/- rats for DMPK and physiological function research. (2) 3D organoids of mouse and human small intestine, a new model to study the function of ABC (P-gp, BCRP, MRP2) transporters. These innovative animal models and organoid models not only help to evaluate the role of drug metabolic enzymes and transporters in DMPK, but also help to deeply understand their functions in normal physiological activities.