Andrean Daniele, Da Ros Francesco, Mazzucato Mario, Pedersen Morten Gram, Visentin Roberto
Department of Information Engineering, University of Padova, Via Giovanni Gradenigo 6b, 35131, Padova, Italy.
CRO Aviano, National Cancer Institute, IRCCS, Via Franco Gallini 2, 33081, Aviano, Italy.
Biol Direct. 2025 Mar 21;20(1):33. doi: 10.1186/s13062-025-00626-x.
Doxorubicin (DOXO) is a well-known chemotherapy drug, which is widely used in the treatment of Multiple Myeloma (MM), a treatable but not curable type of blood cancer. Here, we propose a pharmacokinetics and pharmacodynamics (PK/PD) simulation environment, aimed at facilitating the optimization of DOXO treatment regimens in MM treatment. The resulting model has a transparent mechanistic structure, which facilitates its use and interpretation. The simulator was developed using a combination of experimental and modeling techniques, starting from in vitro PK/PD experiments conducted on MM cells. In our previous work, we carefully developed a PK model for DOXO in MM cells by fitting experimental data. We now devise a PD model from in vitro data investigating the effect of different concentrations of DOXO on cell growth and death in MM cell populations. The PK model is extended to enable a clear mechanistic link between the PK and the PD models, hence providing a complete PK/PD simulator. We show how the mathematical model can be exploited to simulate different DOXO administration protocols with different dosages, repetitions and exposure times, thus, making it possible to explore the effect of a wide range of treatment protocols easily.
阿霉素（DOXO）是一种著名的化疗药物，广泛用于治疗多发性骨髓瘤（MM），这是一种可治疗但无法治愈的血癌。在此，我们提出了一种药代动力学和药效学（PK/PD）模拟环境，旨在促进MM治疗中DOXO治疗方案的优化。所得模型具有透明的机制结构，便于其使用和解释。该模拟器是结合实验和建模技术开发的，始于对MM细胞进行的体外PK/PD实验。在我们之前的工作中，我们通过拟合实验数据，精心为MM细胞中的DOXO建立了一个PK模型。现在，我们根据体外数据设计了一个PD模型，研究不同浓度的DOXO对MM细胞群体中细胞生长和死亡的影响。PK模型得到扩展，以便在PK和PD模型之间建立清晰的机制联系，从而提供一个完整的PK/PD模拟器。我们展示了如何利用数学模型来模拟不同剂量、重复次数和暴露时间的不同DOXO给药方案，从而能够轻松探索广泛治疗方案的效果。
