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对非侵入性或微创生物监测策略的需求以及用于定量的药代动力学/药效学模型的开发。

The need for non- or minimally-invasive biomonitoring strategies and the development of pharmacokinetic/pharmacodynamic models for quantification.

作者信息

Timchalk Charles, Weber Thomas J, Smith Jordan N

机构信息

Pacific Northwest National Laboratory, Richland, WA 99354, USA.

出版信息

Curr Opin Toxicol. 2017 Jun;4:28-34. doi: 10.1016/j.cotox.2017.03.003.

Abstract

Advancements in Exposure Science involving the development and deployment of biomarkers of exposure and biological response are anticipated to significantly (and positively) influence health outcomes associated with occupational, environmental and clinical exposure to chemicals/drugs. To achieve this vision, innovative strategies are needed to develop multiplex sensor platforms capable of quantifying individual and mixed exposures (i.e. systemic dose) by measuring biomarkers of dose and biological response in readily obtainable (non-invasive) biofluids. Secondly, the use of saliva (alternative to blood) for biomonitoring coupled with the ability to rapidly analyze multiple samples in real-time offers an innovative opportunity to revolutionize biomonitoring assessments. In this regard, the timing and number of samples taken for biomonitoring will not be limited as is currently the case. In addition, real-time analysis will facilitate identification of work practices or conditions that are contributing to increased exposures and will make possible a more rapid and successful intervention strategy. The initial development and application of computational models for evaluation of saliva/blood analyte concentration at anticipated exposure levels represents an important opportunity to establish the limits of quantification and robustness of multiplex sensor systems by exploiting a unique computational modeling framework. The use of these pharmacokinetic models will also enable prediction of an exposure dose based on the saliva/blood measurement. This novel strategy will result in a more accurate prediction of exposures and, once validated, can be employed to assess dosimetry to a broad range of chemicals in support of biomonitoring and epidemiology studies.

摘要

暴露科学的进展,包括暴露生物标志物和生物反应生物标志物的开发与应用,预计将对与职业、环境及临床接触化学物质/药物相关的健康结果产生重大(且积极的)影响。为实现这一愿景,需要创新策略来开发多重传感器平台,该平台能够通过测量易于获取(非侵入性)生物流体中的剂量生物标志物和生物反应,来量化个体暴露和混合暴露(即全身剂量)。其次,使用唾液(替代血液)进行生物监测,再加上能够实时快速分析多个样本的能力,为彻底改变生物监测评估提供了一个创新契机。在这方面,用于生物监测的样本采集时间和数量将不会像目前这样受到限制。此外,实时分析将有助于识别导致暴露增加的工作实践或条件,并使更快速、更成功的干预策略成为可能。用于评估预期暴露水平下唾液/血液分析物浓度的计算模型的初步开发和应用,代表了一个重要机会,即通过利用独特的计算建模框架来确定多重传感器系统的定量极限和稳健性。使用这些药代动力学模型还将能够根据唾液/血液测量结果预测暴露剂量。这一新颖策略将更准确地预测暴露情况,一旦得到验证,可用于评估对多种化学物质的剂量测定,以支持生物监测和流行病学研究。

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