Abstract

1. 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.

2. By means of the Monte Carlo simulation method, pharmacokinetic models from different studies are simulated and analyzed in the range of standard deviations of measured system parameters as well as the range of observed model parameters taken from the comparison studies.

3. The 1000 numerical simulations were performed for every analyzed 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.

4. 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

1. 以前，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）的日剂量以及硝苯地平在患者治疗中的存在是MPA表观清除率（CL / F）变异性的重要预测指标。这项研究旨在确定从类似研究中得出的先前发表的人群药代动力学模型的可靠性。此外，本研究调查了文献中所选人口模型之间的对应关系。

2. 通过蒙特卡罗模拟方法，可以对来自不同研究的药代动力学模型进行仿真和分析，包括测量系统参数的标准偏差范围以及比较研究中观察到的模型参数范围。

3. 为了对每个分析的模型进行1000次数值模拟，以便根据执行的实验的期望值计算出最可能的MPA CL / F值。将我们的结果与其他模型进行拟合，表明硝苯地平的存在如何使MPA CL / F值产生差异。

4. 通过将所选研究的数据测试到我们的模型中，可以获得相似的预期CL / F值范围，这可能证实我们模型的有效性。我们的人群药代动力学研究的结果部分适用于其他研究人员的模型。