Danhof Meindert, de Jongh Joost, De Lange Elizabeth C M, Della Pasqua Oscar, Ploeger Bart A, Voskuyl Rob A
Leiden/Amsterdam Center for Drug Research, Division of Pharmacology, Leiden University, 2300 RA Leiden, The Netherlands.
Annu Rev Pharmacol Toxicol. 2007;47:357-400. doi: 10.1146/annurev.pharmtox.47.120505.105154.
Mechanism-based PK-PD models differ from conventional PK-PD models in that they contain specific expressions to characterize, in a quantitative manner, processes on the causal path between drug administration and effect. This includes target site distribution, target binding and activation, pharmacodynamic interactions, transduction, and homeostatic feedback mechanisms. As the final step, the effects on disease processes and disease progression are considered. Particularly through the incorporation of concepts from receptor theory and dynamical systems analysis, important progress has been made in the field of mechanism-based PK-PD modeling. This has yielded models with much-improved properties for extrapolation and prediction. These models constitute a theoretical basis for rational drug discovery and development.
基于机制的药代动力学-药效学（PK-PD）模型与传统PK-PD模型的不同之处在于，它们包含特定的表达式，以定量方式表征药物给药与效应之间因果路径上的过程。这包括靶部位分布、靶点结合与激活、药效学相互作用、转导和稳态反馈机制。作为最后一步，还要考虑对疾病过程和疾病进展的影响。特别是通过纳入受体理论和动态系统分析的概念，基于机制的PK-PD建模领域取得了重要进展。这产生了具有大大改进的外推和预测特性的模型。这些模型构成了合理药物发现和开发的理论基础。
