Database of pharmacokinetic time-series data and parameters for 144 environmental chemicals

Time
courses of compound concentrations in plasma are used in chemical safety
analysis to evaluate the relationship between external administered doses and
internal tissue exposures. This type of experimental data is rarely available
for the thousands of non-pharmaceutical chemicals to which people may
potentially be unknowingly exposed but is necessary to properly assess the risk
of such exposures. In vitro assays and in silico models are often used to craft
an understanding of a chemical’s pharmacokinetics; however, the certainty of
the quantitative application of these estimates for chemical safety evaluations
cannot be determined without in vivo data for external validation. To address this need, we present a public
database of chemical time-series
concentration data from 567 studies in humans or test animals for 144
environmentally-relevant chemicals and their metabolites (187 analytes total).
All major administration routes are incorporated, with concentrations measured
in blood/plasma, tissues, and excreta . We also include calculated
pharmacokinetic parameters for some studies, and a bibliography of additional
source documents to support future extraction of time-series. In addition to pharmacokinetic model
calibration and validation, these data may be used for analyses of differential
chemical distribution across chemicals, species, doses, or routes, and for
meta-analyses on pharmacokinetic studies.

血浆中化合物浓度的时序数据在化学安全性分析中，被用于评估外部给药剂量与内部组织暴露量之间的关系。此类实验数据对于成千上万种非药物化学品而言鲜有可得，这些化学品人们可能在不经意间暴露其中，但其对于准确评估此类暴露风险却是不可或缺的。体外实验和计算机模拟模型常被用来构建对化学品药代动力学的理解；然而，在缺乏体内数据以进行外部验证的情况下，这些估计的定量应用对于化学安全性评估的确定性尚无法确定。为满足这一需求，我们呈现了一个公开数据库，其中包含了567项关于人类或实验动物的研究中，针对144种环境相关化学品及其代谢物（总计187种分析物）的化学时序浓度数据。所有主要的给药途径均被纳入其中，浓度测量包括血液/血浆、组织和排泄物。此外，我们还包含了部分研究的药代动力学参数计算，以及支持未来时间序列提取的额外源文件参考文献。除了药代动力学模型的校准和验证之外，这些数据还可用于分析不同化学品在化学品、物种、剂量或途径间的分布差异，以及药代动力学研究的荟萃分析。