Institute of Computational Comparative Medicine (ICCM), Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, Kansas 66506.
Department of Mathematics, College of Arts and Sciences, Kansas State University, Manhattan, Kansas 66506.
Toxicol Sci. 2017 Jul 1;158(1):23-35. doi: 10.1093/toxsci/kfx070.
Many physiologically based pharmacokinetic (PBPK) models for environmental chemicals, drugs, and nanomaterials have been developed to aid risk and safety assessments using acslX. However, acslX has been rendered sunset since November 2015. Alternative modeling tools and tutorials are needed for future PBPK applications. This forum article aimed to: (1) demonstrate the performance of 4 PBPK modeling software packages (acslX, Berkeley Madonna, MATLAB, and R language) tested using 2 existing models (oxytetracycline and gold nanoparticles); (2) provide a tutorial of PBPK model code conversion from acslX to Berkeley Madonna, MATLAB, and R language; (3) discuss the advantages and disadvantages of each software package in the implementation of PBPK models in toxicology, and (4) share our perspective about future direction in this field. Simulation results of plasma/tissue concentrations/amounts of oxytetracycline and gold from different models were compared visually and statistically with linear regression analyses. Simulation results from the original models were correlated well with results from the recoded models, with time-concentration/amount curves nearly superimposable and determination coefficients of 0.86-1.00. Step-by-step explanations of the recoding of the models in different software programs are provided in the Supplementary Data. In summary, this article presents a tutorial of PBPK model code conversion for a small molecule and a nanoparticle among 4 software packages, and a performance comparison of these software packages in PBPK model implementation. This tutorial helps beginners learn PBPK modeling, provides suggestions for selecting a suitable tool for future projects, and may lead to the transition from acslX to alternative modeling tools.
许多基于生理学的环境化学物质、药物和纳米材料的药代动力学(PBPK)模型已经被开发出来,以帮助使用 acslX 进行风险和安全评估。然而,acslX 自 2015 年 11 月以来已经过时。未来的 PBPK 应用需要替代的建模工具和教程。本文旨在:(1)使用 2 个现有模型(土霉素和金纳米粒子)演示 4 个 PBPK 建模软件包(acslX、Berkeley Madonna、MATLAB 和 R 语言)的性能;(2)提供从 acslX 到 Berkeley Madonna、MATLAB 和 R 语言的 PBPK 模型代码转换教程;(3)讨论每个软件包在毒理学中实施 PBPK 模型的优缺点,(4)分享我们对该领域未来方向的看法。不同模型的土霉素和金的血浆/组织浓度/量的模拟结果通过线性回归分析进行了直观和统计学比较。原始模型的模拟结果与重新编码模型的结果相关性良好,时间-浓度/量曲线几乎重叠,决定系数为 0.86-1.00。在补充数据中提供了在不同软件程序中对模型进行重新编码的逐步说明。总之,本文提供了在 4 个软件包中对小分子和纳米粒子的 PBPK 模型代码转换的教程,以及这些软件包在 PBPK 模型实现中的性能比较。本教程帮助初学者学习 PBPK 建模,为未来项目选择合适的工具提供建议,并可能导致从 acslX 向替代建模工具的过渡。