计算疗效和安全性方面的最佳药物剂量:NONMEM 中增强的 OptiDose 方法。

IF 2.2 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Freya Bachmann, Gilbert Koch, Robert J Bauer, Britta Steffens, Gabor Szinnai, Marc Pfister, Johannes Schropp
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引用次数: 0

摘要

最近,我们开发了一种最佳用药剂量算法(OptiDose),用于计算任何药物计量学模型在给定剂量情况下的最佳用药剂量。在本研究中,我们对 OptiDose 概念进行了改进,以计算疗效和安全性目标方面的最佳药物剂量。通常,这两个目标的重要性并不相同,但其中一个是首要目标,必须满足,而另一个是次要目标,应在不影响首要目标的前提下尽可能实现。从数学上讲,这导致了状态受限的最优控制问题。本文阐述了如何设置此类问题,并将其转化为可在 NONMEM 中求解的经典无约束最优控制问题。三个不同的优化配料任务说明了所提出的增强型 OptiDose 方法的影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Computing optimal drug dosing regarding efficacy and safety: the enhanced OptiDose method in NONMEM.

Recently, an optimal dosing algorithm (OptiDose) was developed to compute the optimal drug doses for any pharmacometrics model for a given dosing scenario. In the present work, we enhance the OptiDose concept to compute optimal drug dosing with respect to both efficacy and safety targets. Usually, these are not of equal importance, but one is a top priority, that needs to be satisfied, whereas the other is a secondary target and should be achieved as good as possible without failing the top priority target. Mathematically, this leads to state-constrained optimal control problems. In this paper, we elaborate how to set up such problems and transform them into classical unconstrained optimal control problems which can be solved in NONMEM. Three different optimal dosing tasks illustrate the impact of the proposed enhanced OptiDose method.

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来源期刊
CiteScore
4.90
自引率
4.00%
发文量
39
审稿时长
6-12 weeks
期刊介绍: Broadly speaking, the Journal of Pharmacokinetics and Pharmacodynamics covers the area of pharmacometrics. The journal is devoted to illustrating the importance of pharmacokinetics, pharmacodynamics, and pharmacometrics in drug development, clinical care, and the understanding of drug action. The journal publishes on a variety of topics related to pharmacometrics, including, but not limited to, clinical, experimental, and theoretical papers examining the kinetics of drug disposition and effects of drug action in humans, animals, in vitro, or in silico; modeling and simulation methodology, including optimal design; precision medicine; systems pharmacology; and mathematical pharmacology (including computational biology, bioengineering, and biophysics related to pharmacology, pharmacokinetics, orpharmacodynamics). Clinical papers that include population pharmacokinetic-pharmacodynamic relationships are welcome. The journal actively invites and promotes up-and-coming areas of pharmacometric research, such as real-world evidence, quality of life analyses, and artificial intelligence. The Journal of Pharmacokinetics and Pharmacodynamics is an official journal of the International Society of Pharmacometrics.
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