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首页> 外文期刊>Journal of pharmacokinetics and biopharmaceutics >Characterization of the dose-dependent time of peak effect in indirect response models.
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Characterization of the dose-dependent time of peak effect in indirect response models.

机译：间接响应模型中峰值效应的剂量依赖性时间的表征。

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摘要

The general conceptual model for non-steady state pharmacokinetic/pharmacodynamic data includes a distribution phase between the plasma and the biophase compartments, which can be expressed by a link model, and inhibition or stimulation of the production or removal of a mediator, which can be expressed by an indirect response model. The inhibition or the stimulation step modeled by an indirect response model generates dose-dependent time of peak effect. This report provides a mathematical expression for this time of peak effect which is then used to determine how this time depends on dose, the endogenous elimination rate of the mediator, and the pharmacokinetic parameters of the drug. The report then uses this time of peak effect to find the response versus time curve. The mathematical relationship for the time of peak effect and the response vs. time curve are then developed for a cascade of two indirect steps. The approach presented here is easily implemented on a spreadsheet and does not require numerically solving nonlinear differential equations. The approach should help to analyze various issues related to fitting indirect response models to non-steady state pharmacokinetic/pharmacodynamic data, especially, when one is trying to fit data to a cascade of indirect steps.
机译：非稳态药代动力学/药效学数据的一般概念模型包括血浆和生物相区室之间的分布阶段（可以通过链接模型表示），以及抑制或刺激介质产生或去除的过程，可以是用间接响应模型表示。通过间接响应模型建模的抑制或刺激步骤会产生剂量依赖性的峰值效应时间。该报告提供了此峰效应时间的数学表达式，然后可用于确定该时间如何取决于剂量，介质的内源消除率以及药物的药代动力学参数。然后，报告将使用这段时间的峰值效应来找到响应时间曲线。然后，针对两个间接步骤的级联，建立了峰值效应时间与响应与时间曲线的数学关系。这里介绍的方法很容易在电子表格上实现，不需要对非线性微分方程进行数值求解。该方法应有助于分析与将间接响应模型拟合到非稳态药代动力学/药效学数据有关的各种问题，尤其是当人们试图将数据拟合为一系列间接步骤时。

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