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METHOD TO EVALUATE THE SYSTEMIC EXPOSURE IN TOXICOLOGICAL AND PHARMACOLOGICAL STUDIES

机译:评价毒理学和药理学研究中全身暴露的方法

摘要

A method of estimating the average exposure within a population of subjects to a pharmacological substance, administered according to a given protocol, by estimating the area under the concentration curve (AUC), characterised in that the area under the population concentration curve is estimated by the steps of obtaining measurements of the drug concentrations in each of the subjects at any time during the study, independently from the time when measurements of the drug concentration level in the other subjects are being taken; building a hierarchical stochastic model composed of the population and of the individual levels; determining the posterior probability distribution of the average AUC from the sample data and hence the average population AUC. The exposure of an individual and its precision within the sample of individuals can be determined by determining the posterior probability distribution of the individual AUC from the sample data. The posterior probability model may be obtained by using a Markov Chain Monte Carlo algorithm, such as Gibbs Sampling.
机译:一种通过给定方案估算受试者群体中平均接触药理物质的方法,方法是估算浓度曲线(AUC)下的面积,其特征在于,人群浓度曲线下的面积通过在研究过程中的任何时间,独立于进行其他受试者药物浓度水平测量的时间,获取每个受试者药物浓度测量值的步骤;建立一个由人口和各个层次组成的分层随机模型;从样本数据中确定平均AUC的后验概率分布,从而确定平均总体AUC。个体的暴露及其在个体样品中的精度可以通过从样品数据确定个体AUC的后验概率分布来确定。可以通过使用诸如吉布斯采样的马尔可夫链蒙特卡洛算法获得后验概率模型。

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