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Robust Control of Repeated Drug Administration with Variable Doses Based on Uncertain Mathematical Model

机译:基于不确定数学模型对可变剂量重复给药的稳健控制

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摘要

The aim of this paper was to design a repeated drug administration strategy to reach and maintain the requested drug concentration in the body. Conservative designs require an exact knowledge of pharmacokinetic parameters, which is considered an unrealistic demand. The problem is usually resolved using the trial-and-error open-loop approach; yet, this can be considered insufficient due to the parametric uncertainties as the dosing strategy may induce an undesired behavior of the drug concentrations. Therefore, the presented approach is rather based on the paradigms of system and control theory. An algorithm was designed that computes the required doses to be administered based on the blood samples. Since repeated drug dosing is essentially a discrete time process, the entire design considers the discrete time domain. We have also presented the idea of applying this methodology for the stabilization of an unstable model, for instance, a model of tumor growth. The simulation experiments demonstrated that all variants of the proposed control algorithm can reach and maintain the desired drug concentration robustly, i.e., despite the presence of parametric uncertainties, in a way that is superior to that of the traditional open-loop approach. It was shown that the closed-loop control with the integral controller and stabilizing state feedback is robust against large parametric uncertainties.
机译:本文的目的是设计一种重复的给药策略,以达到并维持体内所需的药物浓度。保守的设计需要确切的药代动力学参数知识,这被认为是不切实际的要求。该问题通常使用试错开环方法来解决;然而,由于参数的不确定性,这可以被认为是不够的,因为给药策略可能会诱导药物浓度的不良行为。因此,所提出的方法相当基于系统和控制理论的范式。设计了一种算法,根据血液样本计算要给药的所需剂量。由于重复给药本质上是一个离散的时间过程,因此整个设计考虑了离散时域。我们还提出了将这种方法应用于不稳定模型稳定的想法,例如肿瘤生长模型。仿真实验表明,所提出的控制算法的所有变体都可以稳健地达到并保持所需的药物浓度,即尽管存在参数不确定性,但其方式优于传统的开环方法。结果表明,具有积分控制器和稳定状态反馈的闭环控制对较大的参数不确定性是鲁棒的。

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