Haddad S, Pelekis M, Krishnan K
Département de médecine du travail et d'hygiène du milieu, Faculté de médecine, Université de Montréal, Québec, Canada.
Toxicol Lett. 1996 May;85(2):113-26. doi: 10.1016/0378-4274(96)03648-x.
The objective of the present study was to develop and validate a methodology for solving physiologically based pharmacokinetic (PBPK) models without the use of simulation software. The approach involves keying the parameter values and model equations into Microsoft Excel spreadsheets, and conducting simulations by solving the model equations according to Euler's method of numerical integration. This approach was applied to simulate the pharmacokinetics of styrene in rats exposed to 80 and 600 ppm for 6 h. The simulation results were plotted along with experimental data using the regular graphic features available in Excel, and validated by comparing them with simulation results obtained using a commercially available software (Advanced Continuous Simulation Language, ACSL). The simulations obtained with ACSL and Excel, in general, differed by <1%. The methodology developed in the present study should help informed individuals understand and solve PBPK models, without having to use "black-box' kind of computer programs and simulation softwares.
本研究的目的是开发并验证一种无需使用模拟软件来求解基于生理的药代动力学（PBPK）模型的方法。该方法包括将参数值和模型方程输入到Microsoft Excel电子表格中，并根据欧拉数值积分法求解模型方程来进行模拟。将此方法应用于模拟大鼠暴露于80 ppm和600 ppm苯乙烯6小时后的药代动力学。利用Excel中可用的常规图形功能将模拟结果与实验数据一起绘制，并通过与使用市售软件（高级连续模拟语言，ACSL）获得的模拟结果进行比较来进行验证。通常，用ACSL和Excel获得的模拟结果相差<1%。本研究中开发的方法应有助于有相关知识的人员理解和求解PBPK模型，而无需使用“黑箱”式的计算机程序和模拟软件。
