Characterization of drug efficacy regions based on dosage and frequency schedules.
Characterization of drug efficacy regions based on dosage and frequency schedules.
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根据剂量和频率方案表征药物功效区域。
DOI：
10.1109/tbme.2010.2090660
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Dougherty,EdwardR
中科院分区：
文献类型：
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作者：
Li,XiangfangLindsey;Qian,Lijun;Bittner,MichaelL;Dougherty,EdwardR
本文提出了一个框架，以研究药物的作用在分子水平上，以解决以下问题的当前利益的药物社区：给定一个固定的总交付的药物，这是更好的，频繁的小或罕见的大药物剂量？提出了一种混合系统模型，将药物的药代动力学和药效学信息联系起来，并允许对不同剂量和治疗方案的药物效应进行比较。混合模型有助于对导致离散过渡的连续定量变化进行建模。当药物被设计为控制靶基因时，通过分析得到了药物有效的最佳剂量-频率方案和充分必要条件。然后，我们将分析扩展到目标基因是遗传调节网络的一部分的情况。一个关键的观察是，存在一个“甜蜜点”，定义为“药效区（DER）”，在本文中，对于某些剂量和频率的安排给予总的药物。本文量化了DER范围内给药方案的治疗效益。使用MATLAB/SIMULINK进行仿真，以验证分析结果。
This paper proposes a framework to study the drug effect at the molecular level in order to address the following question of current interest in the drug community: Given a fixed total delivered drug, which is better, frequent small or infrequent large drug dosages? A hybrid system model is proposed to link the drug's pharmacokinetic and pharmacodynamic information, and allows the drug effects for different dosages and treatment schedules to be compared. A hybrid model facilitates the modeling of continuous quantitative changes that leads to discrete transitions. An optimal dosage-frequency regimen and the necessary and sufficient conditions for the drug to be effective are obtained analytically when the drug is designed to control a target gene. Then, we extend the analysis to the case where the target gene is part of a genetic regulatory network. A crucial observation is that there exists a “sweet spot,” defined as the “drug efficacy region (DER)” in this paper, for certain dosage and frequency arrangements given the total delivered drug. This paper quantifies the therapeutic benefits of dosage regimen lying within the DER. Simulations are performed using MATLAB/SIMULINK to validate the analytical results.