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使用蒙特卡洛数值分析评估药代动力学霉酚酸清除模型。

Assessment of pharmacokinetic mycophenolic acid clearance models using Monte Carlo numerical analysis.

作者信息

Catić-Đorđević Aleksandra, Pavlović Ivan, Spasić Ana, Stefanović Nikola, Pavlović Dragana, Damnjanović Ivana, Mitić Branka, Veličković-Radovanović Radmila

机构信息

Faculty of Medicine, University of Nis, Nis, Serbia.

Faculty of Mechanical Engineering, University of Nis, Nis, Serbia.

出版信息

Xenobiotica. 2021 Apr;51(4):387-393. doi: 10.1080/00498254.2020.1871532. Epub 2021 Jan 24.

Abstract

Previously, we performed population pharmacokinetic analysis and indicated age, mycophenolate mofetil (MMF)/mycophenolic acid (MPA) daily dose, and presence of nifedipine in patient therapy as significant predictors of MPA apparent clearance (CL/F) variability. This study aimed to determine the reliability of previously published population pharmacokinetic models derived from similar studies. Furthermore, this study investigated correspondence between chosen population models from the literature.By means of the Monte Carlo simulation method, pharmacokinetic models from different studies are simulated and analysed in the range of standard deviations of measured system parameters as well as the range of observed model parameters taken from the comparison studies.The 1000 numerical simulations were performed for every analysed model in order to calculate the most possible MPA CL/F values according to the expected values from the performed experiment. Fitting our results with other models showed how the presence of nifedipine makes difference in MPA CL/F values.By testing the data from selected studies into our model, a similar range of expected CL/F values was obtained, which may confirm the validity of our model. The results of our population pharmacokinetic study are partially applicable in models by other researchers.

摘要

此前,我们进行了群体药代动力学分析,并指出年龄、霉酚酸酯(MMF)/霉酚酸(MPA)日剂量以及患者治疗中是否使用硝苯地平是MPA表观清除率(CL/F)变异性的重要预测因素。本研究旨在确定先前发表的来自类似研究的群体药代动力学模型的可靠性。此外,本研究还调查了文献中所选群体模型之间的一致性。通过蒙特卡罗模拟方法,在测量系统参数的标准差范围内以及从比较研究中获取的观察模型参数范围内,对来自不同研究的药代动力学模型进行模拟和分析。为了根据所进行实验的预期值计算最可能的MPA CL/F值,对每个分析模型进行了1000次数值模拟。将我们的结果与其他模型进行拟合,结果显示硝苯地平的存在如何影响MPA CL/F值。通过将所选研究的数据输入我们的模型进行测试,获得了类似范围的预期CL/F值,这可能证实了我们模型的有效性。我们群体药代动力学研究的结果部分适用于其他研究人员的模型。

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