Genomic Signal Processing Laboratory, Department of Electrical and Computer Engineering, Texas A&M University, College Station, TX 77843, USA.
IEEE Trans Biomed Eng. 2011 Mar;58(3):488-98. doi: 10.1109/TBME.2010.2090660. Epub 2010 Nov 9.
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.
本文提出了一个在分子水平上研究药物作用的框架，以解决当前药物研究领域关注的以下问题：在固定的总给药量下，频繁的小剂量给药和不频繁的大剂量给药哪种更好？本文提出了一种混合系统模型来连接药物的药代动力学和药效学信息，并允许比较不同剂量和治疗方案的药物作用。混合模型有助于对导致离散跃迁的连续定量变化进行建模。当药物被设计用于控制靶基因时，可以分析得到最优的剂量-频率方案和药物有效的必要和充分条件。然后，我们将分析扩展到靶基因是遗传调控网络的一部分的情况。一个关键的观察结果是，在给定总给药量的情况下，存在一个“最佳点”，本文将其定义为“药物疗效区域（DER）”。本文量化了处于 DER 内的剂量方案的治疗益处。使用 MATLAB/SIMULINK 进行了模拟，以验证分析结果。
