The aim of the present study is to develop and implement a methodology that accounts for parameter variability and uncertainty in the presence of qualitative and semi-quantitative information (fuzzy simulations) as well as when some parameters are better quantitatively defined than others (fuzzy-probabilistic approach). The fuzzy simulations method consists of (i) representing parameter uncertainty and variability by fuzzy numbers and (ii) simulating predictions by solving the pharmacokinetic model. The fuzzy-probabilistic approach includes an additional transformation between fuzzy numbers and probability density functions. To illustrate the proposed method a diazepam WBPBPK model was used where the information for hepatic intrinsic clearance determined by in vitro-in vivo scaling was semi-quantitative. The predicted concentration time profiles were compared with those resulting from a Monte Carlo simulation. Fuzzy simulations can be used as an alternative to Monte Carlo simulation.

中文翻译：

---

药代动力学模型的模糊仿真：以地西epa为基础的全身生理学模型的案例研究。

本研究的目的是开发和实施一种方法，该方法在存在定性和半定量信息（模糊模拟）以及某些参数的定量定义优于其他参数（模糊概率）的情况下解决参数可变性和不确定性的问题。方法）。模糊模拟方法包括（i）用模糊数表示参数的不确定性和可变性，以及（ii）通过求解药代动力学模型模拟预测。模糊概率方法包括模糊数和概率密度函数之间的附加转换。为了说明所提出的方法，使用了地西epaWBPBPK模型，其中通过体外-体内定标确定的肝脏固有清除率信息是半定量的。将预测的浓度时间曲线与由蒙特卡洛模拟得出的结果进行比较。模糊模拟可以替代蒙特卡洛模拟。