基于生理学的纳米颗粒药代动力学模型。
Physiologically Based Pharmacokinetic Modeling of Nanoparticles.
机构信息
Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.
China Pharmaceutical University, Nanjing, China.
出版信息
J Pharm Sci. 2019 Jan;108(1):58-72. doi: 10.1016/j.xphs.2018.10.037. Epub 2018 Oct 29.
Nanoparticles are frequently designed to improve the pharmacokinetics profiles and tissue distribution of small molecules to prolong their systemic circulation, target specific tissue, or widen the therapeutic window. The multifunctionality of nanoparticles is frequently presented as an advantage but also results in distinct and complicated in vivo disposition properties compared with a conventional formulation of the same molecules. Physiologically based pharmacokinetic (PBPK) modeling has been a useful tool in characterizing and predicting the systemic disposition, target exposure, and efficacy and toxicity of various types of drugs when coupled with pharmacodynamic modeling. Here we review the unique disposition characteristics of nanoparticles, assess how PBPK modeling takes into account the unique disposition properties of nanoparticles, and comment on the applications and challenges of PBPK modeling in characterizing and predicting the disposition and biological effects of nanoparticles.
纳米粒子通常被设计用于改善小分子的药代动力学特征和组织分布，以延长其体内循环时间、靶向特定组织或拓宽治疗窗口。纳米粒子的多功能性通常被视为优势，但与相同分子的常规制剂相比，也会导致明显而复杂的体内处置特性。生理相关药代动力学（PBPK）模型已成为一种有用的工具，可用于结合药效动力学模型，对各种类型药物的全身处置、靶器官暴露以及疗效和毒性进行特征描述和预测。在这里，我们综述了纳米粒子的独特处置特征，评估了 PBPK 模型如何考虑纳米粒子的独特处置特性，并对 PBPK 模型在特征描述和预测纳米粒子的处置和生物学效应中的应用和挑战进行了评论。
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