Rapid In Vitro Assessment of Antimicrobial Drug Effect Bridging Clinically Relevant Pharmacokinetics: A Comprehensive Methodology.

Rapid In Vitro Assessment of Antimicrobial Drug Effect Bridging Clinically Relevant Pharmacokinetics: A Comprehensive Methodology.
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DOI:
10.3390/pharmaceutics15061671
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发表时间:
2023-06-07
期刊:
影响因子:
5.4
通讯作者:
Tam VH
Tam VH
中科院分区:
医学2区
文献类型:
--
作者:
Nikolaou M;Tam VH

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在临床相关药代动力学条件下快速体外评估抗微生物药物疗效是药物开发和临床使用的基本要素。在这里,我们提出了一个全面的概述,最近开发的一种新的综合方法,用于快速评估这种疗效,特别是对耐药菌株的出现,由作者在最近几年共同研究。这种方法能够在临床相关的药代动力学之后,快速体外评估单一或多种药物组合的抗微生物功效。所提出的方法需要(a)在光密度仪器中自动收集纵向时间杀灭数据;(B)借助数学模型处理收集的时间杀灭数据,以确定单一或多种药物在临床相关药代动力学下的最佳给药方案;以及(c)在中空纤维系统中体外验证有前途的给药方案。通过一些体外研究,这种方法的概念验证进行了讨论。最佳数据收集和处理的完善未来的方向进行了讨论。
Rapid in vitro assessment of antimicrobial drug efficacy under clinically relevant pharmacokinetic conditions is an essential element of both drug development and clinical use. Here, we present a comprehensive overview of a recently developed novel integrated methodology for rapid assessment of such efficacy, particularly against the emergence of resistant bacterial strains, as jointly researched by the authors in recent years. This methodology enables rapid in vitro assessment of the antimicrobial efficacy of single or multiple drugs in combination, following clinically relevant pharmacokinetics. The proposed methodology entails (a) the automated collection of longitudinal time–kill data in an optical-density instrument; (b) the processing of collected time–kill data with the aid of a mathematical model to determine optimal dosing regimens under clinically relevant pharmacokinetics for single or multiple drugs; and (c) in vitro validation of promising dosing regimens in a hollow fiber system. Proof-of-concept of this methodology through a number of in vitro studies is discussed. Future directions for the refinement of optimal data collection and processing are discussed.
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