Laboratory of Clinical Pharmacology and Pharmacometrics, Graduate School of Pharmaceutical Sciences, Chiba University.
Chem Pharm Bull (Tokyo). 2020 Sep 1;68(9):891-894. doi: 10.1248/cpb.c20-00236. Epub 2020 Jul 1.
In pharmacokinetic (PK) analysis, conventional models are described by ordinary differential equations (ODE) that are generally solved in their Laplace transformed forms. The solution in the Laplace transformed forms is inverse Laplace transformed to derive an analytical solution. However, inverse Laplace transform is often mathematically difficult. Consequently, numerical inverse Laplace transform methods have been developed. In this study, we focus on extending the modeling functions of Nonlinear Mixed Effect Model (NONMEM), a standard software for PK and population pharmacokinetic (PPK) analyses, by adding the Fast Inversion of Laplace Transform (FILT) method, one of the representative numerical inverse Laplace transform methods. We implemented PREDFILT, a specialized PRED subroutine, which functions as an internal model unit in NONMEM to enable versatile FILT analysis with second-order precision. The calculation results of the compartment models and a dispersion model are in good agreement with the ordinary analytical solutions and theoretical values. Therefore, PREDFILT ensures enhanced flexibility in PK or PPK analyses under NONMEM environments.
在药代动力学（PK）分析中，传统模型由常微分方程（ODE）描述，通常以拉普拉斯变换形式求解。拉普拉斯变换形式的解通过拉普拉斯逆变换得出解析解。然而，拉普拉斯逆变换在数学上常常很困难。因此，已经开发了数值拉普拉斯逆变换方法。在这项研究中，我们专注于通过添加 Fast Inversion of Laplace Transform（FILT）方法来扩展 NONMEM 的建模函数，NONMEM 是用于 PK 和群体药代动力学（PPK）分析的标准软件，FILT 方法是一种有代表性的数值拉普拉斯逆变换方法。我们实现了 PREDFILT，这是一个专门的 PRED 子例程，它在 NONMEM 中作为内部模型单元，可实现具有二阶精度的多功能 FILT 分析。房室模型和散布模型的计算结果与普通解析解和理论值非常吻合。因此，PREDFILT 确保了 NONMEM 环境下 PK 或 PPK 分析的灵活性增强。
