Ramanathan Murali
Department of Pharmaceutical Sciences, State University of New York at Buffalo, 14260-1200, USA.
Pharm Res. 2002 Oct;19(10):1544-8. doi: 10.1023/a:1020421119533.
The purpose of this study was to evaluate the ability of the dispersion model to describe pharmacokinetic-pharmacodynamic data containing contributions from signal transduction cascades.
The partial differential equations and appropriate boundary conditions describing the dispersion model for signal transduction were obtained. Explicit analytical solutions to the dispersion equation were not available, and a numerical approach was necessary. Solutions were obtained by numerical inversion of the output Laplace transform. Generalized least square fitting was used to obtain parameter estimates for a variety of experimental data sets.
The parameters of the dispersion model estimate the relative roles of diffusion, convection, and chemical reaction in signal transduction. The model is capable of describing messenger RNA and protein expression kinetics induced by drug action.
The dispersion model may find potential applications in pharmacokinetic-pharmacodynamic models involving delayed drug effects mediated by transcriptional changes.
本研究的目的是评估弥散模型描述包含信号转导级联贡献的药代动力学-药效学数据的能力。
获得了描述信号转导弥散模型的偏微分方程和适当的边界条件。弥散方程没有显式解析解，因此需要采用数值方法。通过对输出拉普拉斯变换进行数值反演获得解。使用广义最小二乘法拟合来获得各种实验数据集的参数估计值。
弥散模型的参数估计了扩散、对流和化学反应在信号转导中的相对作用。该模型能够描述药物作用诱导的信使核糖核酸和蛋白质表达动力学。
弥散模型可能在涉及由转录变化介导的延迟药物效应的药代动力学-药效学模型中找到潜在应用。
