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干血斑技术在抗癌药物治疗药物监测中的应用:血浆与干血斑浓度相关的换算方法综述。

Dried Blood Spot Technique Applied in Therapeutic Drug Monitoring of Anticancer Drugs: a Review on Conversion Methods to Correlate Plasma and Dried Blood Spot Concentrations.

机构信息

Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Via Franco Gallini 2, 33081, Aviano, PN, Italy.

Department of Chemical and Pharmaceutical Sciences, University of Trieste, Via Licio Giorgieri 1, 34127, Trieste, Italy.

出版信息

Pharm Res. 2021 May;38(5):759-778. doi: 10.1007/s11095-021-03036-6. Epub 2021 Apr 12.

Abstract

BACKGROUND

Anticancer drugs are notoriously characterized by a low therapeutic index, the introduction of therapeutic drug monitoring (TDM) in oncologic clinical practice could therefore be fundamental to improve treatment efficacy. In this context, an attractive technique to overcome the conventional venous sampling limits and simplify TDM application is represented by dried blood spot (DBS). Despite the significant progress made in bioanalysis exploiting DBS, there is still the need to tackle some challenges that limit the application of this technology: one of the main issues is the comparison of drug concentrations obtained from DBS with those obtained from reference matrix (e.g., plasma). In fact, the use of DBS assays to estimate plasma concentrations is highly dependent on the chemical-physical characteristics of the measured analyte, in particular on how these properties determine the drug partition in whole blood.

METHODS

In the present review, we introduce a critical investigation of the DBS-to-plasma concentration conversion methods proposed in the last ten years and applied to quantitative bioanalysis of anticancer drugs in DBS matrix. To prove the concordance between DBS and plasma concentration, the results of statistical tests applied and the presence or absence of trends or biases were also considered.

摘要

背景

抗癌药物的治疗指数通常较低,因此在肿瘤临床实践中引入治疗药物监测(TDM)可能对于提高治疗效果至关重要。在这种情况下,一种有吸引力的技术可以克服常规静脉采样的限制并简化 TDM 的应用,这就是干血斑(DBS)。尽管利用 DBS 进行生物分析取得了重大进展,但仍需要解决一些限制该技术应用的挑战:其中一个主要问题是比较从 DBS 获得的药物浓度与从参考基质(例如血浆)获得的药物浓度。事实上,使用 DBS 测定法来估计血浆浓度高度依赖于所测分析物的理化特性,特别是这些特性如何决定药物在全血中的分配。

方法

在本综述中,我们批判性地研究了过去十年中提出的用于将 DBS 转换为血浆浓度的方法,并将其应用于 DBS 基质中抗癌药物的定量生物分析。为了证明 DBS 与血浆浓度之间的一致性,还考虑了应用的统计检验结果以及是否存在趋势或偏差。

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