Choi Sung-Min, Kang Chin-Yang, Lee Beom-Jin, Park Jun-Bom
College of Pharmacy, Sahmyook University, Seoul 139-742. Korea.
College of Pharmacy, Ajou University, Suwon 443-749. Korea.
Curr Drug Metab. 2017;18(11):973-982. doi: 10.2174/1389200218666171031124347.
Recently, pharmaceutical research has focused on in vitro-in vivo correlation as a novel challenge, and in silico modeling has been an important component. As in silico models are highly representative of practical use, regulatory agencies such as the US Food and Drug Administration and European Medicines Agency have recognized and utilized in silico modeling as a useful tool; this allows pharmaceutical organizations to use Physiologically Based Pharmacokinetic (PBPK) models for decision-making, which may aid the financial efficiency of a clinical trial. However, some studies have shown differences of up to approximately 40% in pharmacokinetic parameters such as area under the curve or maximum serum concentration between observed and simulated data.
Gastroplus™ was used to demonstrate current PBPK simulation. 46 research papers were compared with each other's applications of PBPK simulation.
To improve the accuracy of simulation, additional factors may need to be considered, such as precise volume of gastrointestinal sections, specific metabolism of the target drug, and physicochemical data of drug metabolites. Furthermore, the results of these simulations would be extremely valuable to the relevant applications. Simulation programs using Advanced Compartmental Absorption and Transit (ACAT)/PBPK modeling could be a powerful tool for companies performing pre-clinical experiments, and could provide a solution for the ethical issues and economic constraints of clinical trials.
If in silico modeling produced more precise results that could closely match clinical data, it could be more readily used to screen drug pharmacodynamics in bodily systems, and the efficiency of clinical trials would be improved. However, simulation programs are currently limited in their accuracy of pharmacodynamic predictions. In developing new drugs, pharmaceutical companies should address this issue in order to improve in silico/PBPK modeling in the future.
最近，药物研究聚焦于体外-体内相关性这一全新挑战，而计算机模拟已成为其中的重要组成部分。由于计算机模拟高度代表实际应用，美国食品药品监督管理局和欧洲药品管理局等监管机构已认可并将计算机模拟用作有用工具；这使得制药机构能够使用基于生理的药代动力学（PBPK）模型进行决策，这可能有助于提高临床试验的财务效率。然而，一些研究表明，在诸如曲线下面积或最大血清浓度等药代动力学参数方面，观察数据与模拟数据之间的差异高达约40%。
使用Gastroplus™软件来演示当前的PBPK模拟。对46篇研究论文中PBPK模拟的应用情况进行了相互比较。
为提高模拟的准确性，可能需要考虑其他因素，如胃肠道各段的精确容积、目标药物的特定代谢以及药物代谢物的理化数据。此外，这些模拟结果对于相关应用将极具价值。使用高级房室吸收与转运（ACAT）/PBPK建模的模拟程序可能是进行临床前实验的公司的有力工具，并且可以为临床试验的伦理问题和经济限制提供解决方案。
如果计算机模拟能产生更精确的结果，使其与临床数据紧密匹配，那么它将更易于用于筛选身体系统中的药物药效学，并且临床试验的效率将会提高。然而，目前模拟程序在药效学预测的准确性方面存在局限性。在开发新药时，制药公司应解决这一问题，以便在未来改进计算机模拟/PBPK建模。
