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测量、模型预测和人血浆中柠檬酸铈清除率的不确定性量化。

Measurement, model prediction and uncertainty quantification of plasma clearance of cerium citrate in humans.

机构信息

Institute of Radiation Medicine, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstrasse 1, 85764, Neuherberg, Germany.

Institute of Resource Ecology, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstraße 400, 01328, Dresden, Germany.

出版信息

Radiat Environ Biophys. 2020 Mar;59(1):121-130. doi: 10.1007/s00411-019-00823-z. Epub 2019 Nov 29.

Abstract

Double tracer studies in healthy human volunteers with stable isotopes of cerium citrate were performed with the aim of investigating the gastro-intestinal absorption of cerium (Ce), its plasma clearance and urinary excretion. In the present work, results of the clearance of Ce in blood plasma are shown after simultaneous intravenous and oral administration of a Ce tracer. Inductively coupled plasma mass spectrometry was used to determine the tracer concentrations in plasma. The results show that about 80% of the injected Ce citrate cleared from the plasma within the 5 mins post-administration. The data obtained are compared to a revised biokinetic model of Ce, which was initially developed by the International Commission on Radiological Protection (ICRP). The measured plasma clearance of Ce citrate was mostly consistent with that predicted by the ICRP biokinetic model. Furthermore, in an effort to quantify the uncertainty of the model prediction, the laboratory animal data on which the ICRP biokinetic Ce model is based, was analyzed. The measured plasma clearance and its uncertainty was also compared to the plasma clearance uncertainty predicted by the model. It was found that the measured plasma clearance during the first 15 min after administration is in a good agreement with the modelled plasma clearance. In general, the measured clearance falls inside the 95% confidence interval predicted by the biokinetic model.

摘要

在健康志愿者中使用稳定同位素的柠檬酸铈进行双示踪剂研究,旨在研究铈(Ce)的胃肠道吸收、其血浆清除率和尿排泄。在本工作中,展示了同时静脉内和口服铈示踪剂后血液中 Ce 的清除率的结果。电感耦合等离子体质谱法用于测定血浆中的示踪剂浓度。结果表明,约 80%的静脉注射的柠檬酸铈在给药后 5 分钟内从血浆中清除。将获得的数据与国际辐射防护委员会(ICRP)最初开发的铈的修订生物动力学模型进行比较。测量的柠檬酸铈血浆清除率与 ICRP 生物动力学模型预测的清除率基本一致。此外,为了量化模型预测的不确定性,分析了基于 ICRP 生物动力学 Ce 模型的实验室动物数据。还将测量的血浆清除率及其不确定性与模型预测的血浆清除率不确定性进行了比较。结果发现,在给药后 15 分钟内测量的血浆清除率与模型预测的血浆清除率吻合良好。总体而言,测量的清除率在生物动力学模型预测的 95%置信区间内。

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