Danhof Meindert, de Lange Elizabeth C M, Della Pasqua Oscar E, Ploeger Bart A, Voskuyl Rob A
Leiden University, Leiden-Amsterdam Center for Drug Research, Division of Pharmacology, Einsteinweg 55, PO Box 9503, 2300 RA Leiden, The Netherlands.
Trends Pharmacol Sci. 2008 Apr;29(4):186-91. doi: 10.1016/j.tips.2008.01.007. Epub 2008 Mar 18.
The use of pharmacokinetic-pharmacodynamic (PK-PD) modeling in translational drug research is a promising approach that provides better understanding of drug efficacy and safety. It is applied to predict efficacy and safety in humans using in vitro bioassay and/or in vivo animal data. Current research in PK-PD modeling focuses on the development of mechanism-based models with improved extrapolation and prediction properties. A key element in mechanism-based PK-PD modeling is the explicit distinction between parameters for describing (i) drug-specific properties and (ii) biological system-specific properties. Mechanism-based PK-PD models contain specific expressions for the characterization of processes on the causal path between drug exposure and drug response. The different terms represent: target-site distribution, target binding and activation and transduction. Ultimately, mechanism-based PK-PD models will also characterize the interaction of the drug effect with disease processes and disease progression. In this review, the principles of mechanism-based PK-PD modeling are described and illustrated by recent applications.
药代动力学-药效学（PK-PD）模型在转化药物研究中的应用是一种很有前景的方法，它能更好地理解药物的疗效和安全性。该模型通过体外生物测定和/或体内动物数据来预测人体中的疗效和安全性。目前PK-PD模型的研究重点是开发具有改进的外推和预测特性的基于机制的模型。基于机制的PK-PD建模的一个关键要素是明确区分用于描述（i）药物特异性特性和（ii）生物系统特异性特性的参数。基于机制的PK-PD模型包含用于表征药物暴露与药物反应之间因果路径上过程的特定表达式。不同的术语代表：靶点部位分布、靶点结合与激活以及转导。最终，基于机制的PK-PD模型还将表征药物效应与疾病过程和疾病进展之间的相互作用。在本综述中，基于机制的PK-PD建模原理将通过近期应用进行描述和说明。
