Zhou Zhengying, Zhu Jinwei, Jiang Muhan, Sang Lan, Hao Kun, He Hua
Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
State Key Laboratory of Natural Medicines, Jiangsu Province Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
Pharmaceutics. 2021 May 12;13(5):704. doi: 10.3390/pharmaceutics13050704.
Human-derived in vitro models can provide high-throughput efficacy and toxicity data without a species gap in drug development. Challenges are still encountered regarding the full utilisation of massive data in clinical settings. The lack of translated methods hinders the reliable prediction of clinical outcomes. Therefore, in this study, in silico models were proposed to tackle these obstacles from in vitro to in vivo translation, and the current major cell culture methods were introduced, such as human-induced pluripotent stem cells (hiPSCs), 3D cells, organoids, and microphysiological systems (MPS). Furthermore, the role and applications of several in silico models were summarised, including the physiologically based pharmacokinetic model (PBPK), pharmacokinetic/pharmacodynamic model (PK/PD), quantitative systems pharmacology model (QSP), and virtual clinical trials. These credible translation cases will provide templates for subsequent in vitro to in vivo translation. We believe that synergising high-quality in vitro data with existing models can better guide drug development and clinical use.
在药物研发中，人源体外模型能够提供高通量的药效和毒性数据，且不存在种属差异。然而，在临床环境中充分利用海量数据仍面临挑战。缺乏可转化的方法阻碍了对临床结果的可靠预测。因此，在本研究中，我们提出了计算机模拟模型，以解决从体外到体内转化过程中的这些障碍，并介绍了当前主要的细胞培养方法，如人诱导多能干细胞（hiPSC）、3D细胞、类器官和微生理系统（MPS）。此外，总结了几种计算机模拟模型的作用和应用，包括基于生理的药代动力学模型（PBPK）、药代动力学/药效学模型（PK/PD）、定量系统药理学模型（QSP）和虚拟临床试验。这些可靠的转化案例将为后续的体外到体内转化提供模板。我们相信，将高质量的体外数据与现有模型相结合，可以更好地指导药物研发和临床应用。
