COMPARISON OF 3 PHYSIOLOGICALLY BASED PHARMACOKINETIC MODELS OF BENZENE DISPOSITION
COMPARISON OF 3 PHYSIOLOGICALLY BASED PHARMACOKINETIC MODELS OF BENZENE DISPOSITION
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DOI：
10.1016/0041-008x(91)90291-l
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发表时间：
1991-08-01
影响因子：
3.8
通讯作者：
SPEAR, RC
中科院分区：
文献类型：
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作者：
BOIS, FY;WOODRUFF, TJ;SPEAR, RC
我们评估了三种基于生理学的苯药代动力学模型与 Fischer-344 大鼠实验数据的拟合优度。这些模型是独立开发和发布的。观察到拟合质量存在很大差异。此外，导致可接受拟合的参数值分布在生理上合理值的整个范围内，并且可能与平均值或标准值有很大不同。另一方面，选择参数的标准值并不能确保对所有组织水平进行良好的预测。这些结果强调了严格校准生理模型的难度，以及该领域进一步研究的必要性，包括参数值的精确实验确定。生理模型是强大的工具，但出于风险评估的目的，更简单的模型（同等地使用关键数据）可能更可取。
We assess the goodness of fit of three physiologically based models of benzene pharmacokinetics to experimental data in Fischer-344 rats. These models were independently developed and published. Large differences in the quality of the fit are observed. In addition, the parameter values leading to acceptable fits are spread over the entire range of physiologically plausible values and can be quite different from average or standard values. On the other hand, choosing standard values for the parameters does not ensure good predictions of all tissue levels. These results emphasize the difficulty of a rigorous calibration of physiological models, and the need for further research in this area, including precise experimental determination of parameter values. Physiological models are powerful tools, but for risk assessment purposes simpler models, making equivalent use of the crucial data, are probably preferable.