Comparison of the use of a physiologically based pharmacokinetic model and a classical pharmacokinetic model for dioxin exposure assessments.
Comparison of the use of a physiologically based pharmacokinetic model and a classical pharmacokinetic model for dioxin exposure assessments.
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比较基于生理的药代动力学模型和用于二恶英暴露评估的经典药代动力学模型的比较。
DOI：
10.1289/ehp.8016
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发表时间：
2005-12
影响因子：
10.4
通讯作者：
中科院分区：
文献类型：
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作者：
在流行病学研究中，2,3,7,8-四氯二苯并-对二恶英（TCDD）的暴露评估假设有固定的消除率。最近的数据表明TCDD的消除率与剂量有关。先前在啮齿动物中开发了基于生理的药代动力学（PBPK）模型，该模型使用依赖于身体负荷的消除率来描述TCDD的药代动力学，并在本研究中外推到人类暴露。优化使用随机选择的牧场手队列退伍军人和暴露于TCDD的人类志愿者的数据进行。对PBPK模型的评估使用了来自Ranch Hand队列的额外数据和两名暴露于TCDD的妇女的临床报告。该PBPK模型表明，以前的暴露评估可能显著低估了峰值血药浓度，从而导致潜在的暴露错误分类。应用包含诱导消除TCDD的PBPK模型可以改善TCDD流行病学研究中的暴露评估。
In epidemiologic studies, exposure assessments of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) assume a fixed elimination rate. Recent data suggest a dose-dependent elimination rate for TCDD. A physiologically based pharmacokinetic (PBPK) model, which uses a body-burden–dependent elimination rate, was developed previously in rodents to describe the pharmacokinetics of TCDD and has been extrapolated to human exposure for this study. Optimizations were performed using data from a random selection of veterans from the Ranch Hand cohort and data from a human volunteer who was exposed to TCDD. Assessment of this PBPK model used additional data from the Ranch Hand cohort and a clinical report of two women exposed to TCDD. This PBPK model suggests that previous exposure assessments may have significantly underestimated peak blood concentrations, resulting in potential exposure misclassifications. Application of a PBPK model that incorporates an inducible elimination of TCDD may improve the exposure assessments in epidemiologic studies of TCDD.