School of Pharmacy, Faculty of Science and Engineering, University of Wolverhampton, City Campus, Wulfruna Street, WV1 1SB, England, United Kingdom; School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, England, United Kingdom.
School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, England, United Kingdom.
Adv Drug Deliv Rev. 2015 Jun 23;86:101-11. doi: 10.1016/j.addr.2015.03.005. Epub 2015 Mar 18.
The use of in silico tools within the drug development process to predict a wide range of properties including absorption, distribution, metabolism, elimination and toxicity has become increasingly important due to changes in legislation and both ethical and economic drivers to reduce animal testing. Whilst in silico tools have been used for decades there remains reluctance to accept predictions based on these methods particularly in regulatory settings. This apprehension arises in part due to lack of confidence in the reliability, robustness and applicability of the models. To address this issue we propose a scheme for the verification of in silico models that enables end users and modellers to assess the scientific validity of models in accordance with the principles of good computer modelling practice. We report here the implementation of the scheme within the Innovative Medicines Initiative project "eTOX" (electronic toxicity) and its application to the in silico models developed within the frame of this project.
由于立法的变化以及减少动物试验的伦理和经济驱动因素，在药物开发过程中使用计算机模拟工具来预测包括吸收、分布、代谢、消除和毒性在内的广泛性质变得越来越重要。尽管计算机模拟工具已经使用了几十年，但人们仍然不愿意接受基于这些方法的预测，特别是在监管环境中。这种担忧部分源于对模型的可靠性、稳健性和适用性缺乏信心。为了解决这个问题，我们提出了一种用于验证计算机模型的方案，使最终用户和建模者能够根据计算机建模良好实践的原则评估模型的科学有效性。我们在这里报告了该方案在创新药物倡议项目“eTOX”（电子毒性）中的实施情况及其在该项目框架内开发的计算机模型中的应用。
