Toxicology and Risk Assessment, Eastman Kodak Company, Rochester, New York, USA.
Toxicol Mech Methods. 2005;15(2):137-54. doi: 10.1080/15376520590918810.
Abstract Physiologically based pharmacokinetic (PBPK) models are mathematical descriptions depicting the relationship between external exposure and internal dose. These models have found great utility for interspecies extrapolation. However, specialized computer software packages, which are not widely distributed, have typically been used for model development and utilization. A few physiological models have been reported using more widely available software packages (e.g., Microsoft Excel), but these tend to include less complex processes and dose metrics. To ascertain the capability of Microsoft Excel and Visual Basis for Applications (VBA) for PBPK modeling, models for styrene, vinyl chloride, and methylene chloride were coded in Advanced Continuous Simulation Language (ACSL), Excel, and VBA, and simulation results were compared. For styrene, differences between ACSL and Excel or VBA compartment concentrations and rates of change were less than +/-7.5E-10 using the same numerical integration technique and time step. Differences using VBA fixed step or ACSL Gear's methods were generally <1.00E-03, although larger differences involving very small values were noted after exposure transitions. For vinyl chloride and methylene chloride, Excel and VBA PBPK model dose metrics differed by no more than -0.013% or -0.23%, respectively, from ACSL results. These differences are likely attributable to different step sizes rather than different numerical integration techniques. These results indicate that Microsoft Excel and VBA can be useful tools for utilizing PBPK models, and given the availability of these software programs, it is hoped that this effort will help facilitate the use and investigation of PBPK modeling.
摘要 生理药代动力学（PBPK）模型是描述外暴露与内剂量之间关系的数学描述。这些模型在种间外推方面具有很大的应用价值。然而，通常用于模型开发和利用的是专门的计算机软件包，这些软件包并未广泛分发。已经有一些生理模型使用更广泛可用的软件包（例如 Microsoft Excel）进行了报道，但这些模型往往包含较少的复杂过程和剂量指标。为了确定 Microsoft Excel 和 Visual Basic for Applications（VBA）用于 PBPK 建模的能力，使用 Advanced Continuous Simulation Language（ACSL）、Excel 和 VBA 对苯乙烯、氯乙烯和二氯甲烷的模型进行了编码，并比较了模拟结果。对于苯乙烯，使用相同的数值积分技术和时间步长，ACSL 与 Excel 或 VBA 隔室浓度和变化率之间的差异小于 +/-7.5E-10。使用 VBA 固定步长或 ACSL Gear 的方法时，差异通常<1.00E-03，尽管在暴露转换后，涉及非常小值的差异较大。对于氯乙烯和二氯甲烷，Excel 和 VBA PBPK 模型剂量指标与 ACSL 结果的差异不超过-0.013%或-0.23%。这些差异可能归因于不同的步长大小，而不是不同的数值积分技术。这些结果表明，Microsoft Excel 和 VBA 可以成为利用 PBPK 模型的有用工具，并且考虑到这些软件程序的可用性，希望这一努力将有助于促进 PBPK 建模的使用和研究。
