单室毒性动力学模型的通用求解

Sandrine Charles,Aude Ratier,Christelle Lopes
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摘要

本文给出了定义单室毒性动力学模型的一类常微分方程的全解析解。这些模型描述了当生物体暴露于化学物质时发生的吸收和消除过程。本文解决的模型将生物体视为一个独特的隔间,母体化合物通过几种可能的暴露途径进入其中,并从中消除其潜在的代谢物。受益于单室毒性动力学模型的通用解在将它们拟合到实验数据时特别有用,有助于编写导致参数估计的推理算法。此外,这些模型在环境风险评估中具有重要意义,用于计算生物积累指标,以支持监管机构在评估原料药上市许可档案时的决策。
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Generic Solving of One-compartment Toxicokinetic Models
This paper gives the full analytical solution of the generic set of ordinary differential equations that define one-compartment toxicokinetic models. These models describe the uptake and elimination processes that occur within living organisms when exposed to chemical substances. The models solved in this paper consider living organisms as a unique compartment, into which a parent compound enters via several possible exposure routes and from which it is eliminated as well as its potential metabolites. Benefiting from generic solutions of one-compartment toxicokinetic models is particularly useful when fitting them to experimental data, facilitating the writing of the inference algorithms leading to parameter estimates. Additionally, these models are of crucial interest in environmental risk assessment for the calculation of bioaccumulation metrics as required by regulators in support of decision-making when they evaluate dossiers for marketing authorisation of active substances.
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