DMPK, In Vitro In Vivo Translation, GSK, Stevenage, UK.
Clinical Pharmacology, Modelling and Simulation, GSK, Stevenage, UK.
Clin Transl Sci. 2022 Mar;15(3):588-600. doi: 10.1111/cts.13183. Epub 2021 Nov 12.
Translational model-based approaches have played a role in increasing success in the development of novel anticancer treatments. However, despite this, significant translational uncertainty remains from animal models to patients. Optimization of dose and scheduling (regimen) of drugs to maximize the therapeutic utility (maximize efficacy while avoiding limiting toxicities) is still predominately driven by clinical investigations. Here, we argue that utilizing pragmatic mechanism-based translational modeling of nonclinical data can further inform this optimization. Consequently, a prototype model is demonstrated that addresses the required fundamental mechanisms.
基于转化模型的方法在提高新型抗癌治疗方法的成功率方面发挥了作用。然而,尽管如此,从动物模型到患者仍然存在很大的转化不确定性。优化药物剂量和方案(方案)以最大限度地提高治疗效果(在避免限制毒性的同时最大限度地提高疗效)仍然主要由临床研究驱动。在这里,我们认为利用非临床数据的实用基于机制的转化建模可以进一步为这种优化提供信息。因此,展示了一个原型模型,该模型解决了所需的基本机制。