生理药动学模型在纳米材料毒理学研究中的应用进展

Application of physiologically based pharmacokinetic model in toxicology of nanomaterials: research advances

以生理学为基础的药动学模型,简称生理药动学(PBPK)模型,是根据现有的人类或其他动物的解剖和生理知识及其生物化学数据建立,通过数学方法模拟化学物质在体内的吸收、分布、代谢和排泄的过程,进而实现剂量外推和种间外推,预测化学物质在特定组织或时间内的剂量水平。在纳米材料的毒理学研究方面,纳米银、纳米氧化锌、纳米二氧化钛以及多聚纳米材料等都逐步建立了PBPK模型。PBPK模型不仅能提供纳米材料在体内动态变化情况,也对定量评价纳米材料的生物安全性具有重要意义,将是纳米材料毒理学研究及安全性评价的发展方向。

Physiologically based pharmacokinetic（PBPK） modeling is established based on the information of existing human or other animal anatomy, knowledge of physiology and biochemical data.The model uses mathematical methods to simulate chemicals′ process of absorption, distribution, metabolism and excretion in the body, in order to achieve the dose and interspecific extrapolation and to predict the chemical level in the specific organ at the specific time.In studies on toxicology of nanomaterials, the PBPK models in the silver nanoparticles, zinc oxide nanoparticles, titanium dioxide nanoparticles and polymer nanomaterials are gradually established.PBPK modeling can not only provide information on the dynamic change of nanomaterials in the body, but is of great significance for to quantitative evaluation of biological safety of nanomaterials.PBPK modeling will be a hot spot for research in the field of nanotoxicology.