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Pitfalls in pharmacokinetic multicompartment analysis.

机译:药代动力学多室分析中的陷阱。

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摘要

When a pharmacokinetic (PK) two-compartment body model with first-order absorption is fitted to blood levels of a drug, the estimates of the PK parameters may have considerable errors and can cause wrong predictions in other features of the system. The objectives of this report were to illustrate this problem, to provide an easy way to prevent wrong estimation, and to investigate the origin of the mistake. A simple way to prevent wrong interpretation of the calculated PK parameters is to inspect the PK profiles visually. Without observing a clear biphasic profile, one should not apply the two-compartment model if the resulting parameters are to be interpreted and used for further simulations. We investigated the origin of this ambiguity in terms of the relative order of magnitude of microconstants (ka, k12, k21, and k10) and of hybrid constants (A and B). The observed parameter errors will not be of any relevance if the calculated parameters are used only to predict future blood levels over the same time-span. However, if these parameters are used to predict any other characteristic of the system, erroneous predictions may result.
机译:当将具有一阶吸收的药代动力学(PK)两室人体模型拟合到药物的血液水平时,PK参数的估计值可能会有相当大的误差,并且可能导致系统其他特征的错误预测。本报告的目的是说明此问题,提供一种防止错误估计并调查错误根源的简便方法。防止错误解释所计算的PK参数的一种简单方法是目视检查PK轮廓。如果没有观察到清晰的双相曲线,则如果要解释生成的参数并将其用于进一步的仿真,则不应使用两室模型。我们根据微常数(ka,k12,k21和k10)和混合常数(A和B)的相对大小顺序研究了这种歧义的起源。如果计算出的参数仅用于预测同一时间范围内的未来血液水平,则观察到的参数误差将没有任何意义。但是,如果将这些参数用于预测系统的任何其他特征,则可能会导致错误的预测。

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