Pharmacokinetic models in the development of exposure indicators in epidemiology.
Pharmacokinetic models in the development of exposure indicators in epidemiology.
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流行病学暴露指标开发中的药代动力学模型。
DOI：
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发表时间：
1991
影响因子：
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通讯作者：
T. Smith
中科院分区：
文献类型：
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作者：
T. Smith
生理药代动力学（PK）模型可以从关于化学剂的血液溶解度、分配系数和代谢率的数据估计组织水平。这些模型在流行病学研究中的使用受到限制。如果满足以下四个条件，PK模型可能是有用的：（1）确定了潜在的致病因子;（2）确定了具有显著不同的暴露强度曲线的受试者组;（3）生理PK模型可用于外推潜在因子的靶组织浓度;以及（4）机制假设预测了组织浓度的不同时间曲线的显著不同风险。这种方法的一个例子是混合碳氢化合物暴露的癌症风险，包括三个实用的剂量指数的发展。这种PK模型的使用产生了对风险评估有用的剂量-反应关系，并且它允许对来自实验室研究的机制假设进行流行病学评价。
Physiological pharmacokinetic (PK) models can estimate tissue levels from data on blood solubility, partition coefficients and metabolic rate(s) of a chemical agent. Use of these models in epidemiological studies has been limited. PK models can be useful if four conditions are met: (1) potential causal agents are identified; (2) groups of subjects with substantially different profiles of exposure intensity are identified; (3) a physiological PK model is available to extrapolate target tissue concentrations for potential agents; and (4) mechanistic hypotheses predict substantially different risk for different time profiles of tissue concentration. An example of this approach is presented for cancer risk from mixed hydrocarbon exposures, including the development of three practical dose indices. This use of PK models produces dose-response relationships useful for risk assessment, and it permits epidemiological evaluation of mechanistic hypotheses derived from laboratory studies.