Scaling pharmacodynamics from in vitro and preclinical animal studies to humans.
Scaling pharmacodynamics from in vitro and preclinical animal studies to humans.
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DOI：
10.2133/dmpk.24.16
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发表时间：
2009
影响因子：
2.1
通讯作者：
Jusko WJ
中科院分区：
文献类型：
--
作者：
Mager DE;Woo S;Jusko WJ
基于机制的药代动力学/药效学（PK/PD）模型的一个重要特征是确定药物和系统特异性因素，这些因素决定了药理作用的强度和时间过程。这为整合从体外生物测定和动物临床前药理学研究中获得的信息提供了机会，以预测人类对药物的临床和不良反应。事实上，当代PK/PD模型不断发展，并寻求模拟系统级属性，应该提供增强的能力，以扩大药效学数据。药物发现和开发的关键步骤，如先导化合物和首次人体剂量选择，可能会随着翻译PK/PD模型的实施和进一步完善而变得更加有效。在这篇综述中，我们强调了药效学的基本原理和体外生物测定的基本期望和传统的异速标度在PK/PD模型中。讨论重组人促红细胞生成素的PK/PD建模工作也包括作为一个案例研究，显示了先进系统分析的潜力，以促进外推和提高对药物反应的物种间差异的理解。
An important feature of mechanism-based pharmacokinetic/pharmacodynamic (PK/PD) models is the identification of drug- and system-specific factors that determine the intensity and time-course of pharmacological effects. This provides an opportunity to integrate information obtained from in vitro bioassays and preclinical pharmacological studies in animals to anticipate the clinical and adverse responses to drugs in humans. The fact that contemporary PK/PD modeling continues to evolve and seeks to emulate systems level properties should provide enhanced capabilities to scale-up pharmacodynamic data. Critical steps in drug discovery and development, such as lead compound and first in human dose selection, may become more efficient with the implementation and further refinement of translational PK/PD modeling. In this review, we highlight fundamental principles in pharmacodynamics and the basic expectations for in vitro bioassays and traditional allometric scaling in PK/PD modeling. Discussion of PK/PD modeling efforts for recombinant human erythropoietin is also included as a case study showing the potential for advanced systems analysis to facilitate extrapolations and improve understanding of inter-species differences in drug responses.
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DOI：
10.1124/jpet.107.119560
发表时间：
2007-10-01
影响因子：
3.5
作者：
Kalvass, J. Cory;Olson, Emily R.;Pollack, Gary M.
通讯作者：
Pollack, Gary M.
DOI：
10.1023/a:1025728028890
发表时间：
1997-04-01
期刊：
JOURNAL OF PHARMACOKINETICS AND BIOPHARMACEUTICS
影响因子：
--
作者：
Cosson, VF;Fuseau, E;Bye, A
通讯作者：
Bye, A
影响因子：
8.8
作者：
Cox, EH;Langemeijer, MWE;Danhof, M
通讯作者：
Danhof, M
DOI：
10.1007/bf01061691
发表时间：
1993-08-01
期刊：
JOURNAL OF PHARMACOKINETICS AND BIOPHARMACEUTICS
影响因子：
--
作者：
DAYNEKA, NL;GARG, V;JUSKO, WJ
通讯作者：
JUSKO, WJ
影响因子：
3.7
作者：
Hong, Ying;Mager, Donald E.;Jusko, William J.
通讯作者：
Jusko, William J.