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首页> 外文期刊>Journal of applied toxicology >Distinguishing animal subsets in toxicokinetic studies: comparison of non-linear mixed effects modelling with non-compartmental methods.
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Distinguishing animal subsets in toxicokinetic studies: comparison of non-linear mixed effects modelling with non-compartmental methods.

机译：在毒代动力学研究中区分动物子集：比较非混合方法与非线性混合效应模型。

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The purpose of this study was to compare the ability of non-compartmental analysis and compartmental mixed effects modelling (MEM) to determine the existence and magnitude of exposure differences (i.e. exposure ratio estimates) between subsets of animals during destructive toxicokinetic studies. Data from five toxicokinetic studies of an experimental compound were analysed using a linear trapezoidal calculation of the area under the curve (non-compartmental analysis) or modelled using MEM. With the non-compartmental method the Bailer-Satterthwaite approximation was used to construct confidence intervals around the exposure estimates of each subset of animals and these were used to determine if exposure differed between the subsets. The MEM analyses were performed on the full datasets and on datasets with arbitrary reductions in the number of animal replicates. With MEM, additional model parameters were used to differentiate between subsets of animals, and were incorporated only if they were justified statistically. Estimates of the existence and magnitude of exposure differences between animal subsets were similar with the two techniques. The MEM analyses were influenced only marginally by substantial reductions in the number of animals studied and were less compromised by extremely limited or unbalanced data. These analyses show that MEM and non-compartmental methods are similarly effective at detecting exposure differences between animal subsets in toxicokinetic studies. Estimates provided by both methods were influenced by the degree of variance in the data. These results support the proposition that it may be possible to reduce the number of animals employed in toxicokinetic studies if MEM is used.
机译：这项研究的目的是比较非隔室分析和隔室混合效应模型（MEM）的能力，以确定在破坏性毒物代谢动力学研究期间动物子集之间的接触差异（即接触比估计）的存在和大小。使用曲线下面积的线性梯形计算（非隔室分析）来分析来自实验化合物的五次毒代动力学研究的数据（或使用MEM建模）。使用非隔室方法时，使用Bailer-Satterthwaite逼近来构建每个动物子集的暴露估计值周围的置信区间，并使用这些区间来确定子集之间的暴露量是否不同。 MEM分析是在完整数据集和动物复制数量任意减少的数据集上进行的。借助MEM，可以使用其他模型参数来区分动物的子集，并且只有在统计学上合理的情况下才将其纳入。两种技术对动物亚组之间接触差异的存在和大小的估计相似。 MEM分析仅受到研究动物数量大幅减少的轻微影响，而受到极有限或不平衡数据的损害较小。这些分析表明，在代谢动力学研究中，MEM和非房室方法在检测动物亚群之间的暴露差异方面同样有效。两种方法提供的估计值均受数据差异程度的影响。这些结果支持这样的主张，即如果使用MEM，有可能减少在毒代动力学研究中使用的动物数量。

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