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在一个简单的基于生理的药代动力学模型中，使用反向剂量测定法重建有机磷农药剂量。

Reconstructing organophosphorus pesticide doses using the reversed dosimetry approach in a simple physiologically-based pharmacokinetic model.

作者信息

Lu Chensheng, Andres Leo

机构信息

Department of Environmental Health, Harvard School of Public Health, 401 Park Drive, Boston, MA 02215, USA.

出版信息

J Toxicol. 2012;2012:131854. doi: 10.1155/2012/131854. Epub 2012 Feb 1.

DOI:10.1155/2012/131854
PMID:22496685
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3306923/
Abstract

We illustrated the development of a simple pharmacokinetic (SPK) model aiming to estimate the absorbed chlorpyrifos doses using urinary biomarker data, 3,5,6-trichlorpyridinol as the model input. The effectiveness of the SPK model in the pesticide risk assessment was evaluated by comparing dose estimates using different urinary composite data. The dose estimates resulting from the first morning voids appeared to be lower than but not significantly different to those using before bedtime, lunch or dinner voids. We found similar trend for dose estimates using three different urinary composite data. However, the dose estimates using the SPK model for individual children were significantly higher than those from the conventional physiologically based pharmacokinetic (PBPK) modeling using aggregate environmental measurements of chlorpyrifos as the model inputs. The use of urinary data in the SPK model intuitively provided a plausible alternative to the conventional PBPK model in reconstructing the absorbed chlorpyrifos dose.

摘要

我们阐述了一个简单的药代动力学（SPK）模型的开发，该模型旨在利用尿生物标志物数据（3,5,6-三氯吡啶醇作为模型输入）来估算毒死蜱的吸收剂量。通过比较使用不同尿液综合数据的剂量估算值，评估了SPK模型在农药风险评估中的有效性。首次晨尿产生的剂量估算值似乎低于睡前、午餐或晚餐后尿液产生的剂量估算值，但差异不显著。我们发现使用三种不同尿液综合数据进行剂量估算时呈现出类似趋势。然而，使用SPK模型对个体儿童进行的剂量估算显著高于使用毒死蜱总体环境测量值作为模型输入的传统基于生理的药代动力学（PBPK）模型得出的剂量估算值。在重建毒死蜱吸收剂量方面，SPK模型中使用尿液数据直观地为传统PBPK模型提供了一个合理的替代方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23dd/3306923/827d1a8b1a09/JT2012-131854.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23dd/3306923/93c8f2a1a6e5/JT2012-131854.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23dd/3306923/e1ed883ac9d3/JT2012-131854.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23dd/3306923/827d1a8b1a09/JT2012-131854.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23dd/3306923/93c8f2a1a6e5/JT2012-131854.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23dd/3306923/e1ed883ac9d3/JT2012-131854.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23dd/3306923/827d1a8b1a09/JT2012-131854.003.jpg

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