Bayer Technology Services GmbH, Computational Systems Biology, Leverkusen, Germany.
J Pharm Pharmacol. 2012 Jul;64(7):997-1007. doi: 10.1111/j.2042-7158.2012.01534.x. Epub 2012 May 16.
In-silico methods are a cost-effective possibility to support decision making at different stages of the drug development process. Among the various computational methods available, physiologically-based pharmacokinetic (PBPK) modelling represents a well-established tool for mechanistically predicting the pharmacokinetics of drugs and drug candidates. PK-Sim, a component of the Computational Systems Biology Software Suite of Bayer Technology Services GmbH (Leverkusen, Germany) is a commercial PBPK software tool. It is based on a generic model structure for typical animal species from mice to monkey and humans, and allows simultaneous simulation of drug liberation, absorption, distribution, metabolism, and excretion in one model. In this study PK-Sim has been used for the prediction of the in-vivo pharmacokinetics of drugs with a particular focus on the integration of dissolution properties and, due to its leading role in the drug development process, for the performance of different dosage forms administered via the oral route.
Three real life case studies have been presented to exemplify the benefits of using PBPK absorption modelling.
In the first example, the in-vivo dissolution rate was directly predicted from the physical properties of different particle formulations using a mechanistic dissolution model of the Noyes-Whitney type. In the second case study, the PBPK tool was successfully used to predict the food effect in humans based on data obtained in Beagle dogs. In the third example, the utilization of the software for the support of the development of a combined immediate release-controlled release formulation has been described.
Future perspectives of the use of PBPK modelling have been discussed, with a special focus on the integration of in-vitro dissolution data into PBPK models for oral and non-oral administration of drugs.
计算方法是支持药物开发过程不同阶段决策的一种具有成本效益的可能性。在现有的各种计算方法中，基于生理学的药代动力学（PBPK）建模是一种成熟的工具，可用于从机制上预测药物和候选药物的药代动力学。PK-Sim 是拜耳技术服务有限公司（德国勒沃库森）计算系统生物学软件套件的一个组成部分，是一种商业 PBPK 软件工具。它基于一个通用的模型结构，适用于从老鼠到猴子和人类等典型动物物种，并允许在一个模型中同时模拟药物释放、吸收、分布、代谢和排泄。在这项研究中，PK-Sim 用于预测药物的体内药代动力学，特别关注溶解特性的整合，并且由于其在药物开发过程中的主导作用，还用于通过口服途径给予不同剂型的性能。
提出了三个真实案例研究，以举例说明使用 PBPK 吸收模型的好处。
在第一个示例中，使用 Noyes-Whitney 型的机械溶解模型，直接从不同颗粒制剂的物理特性预测体内溶解速率。在第二个案例研究中，成功地使用 PBPK 工具基于比格犬获得的数据预测了人体中的食物效应。在第三个示例中，描述了该软件用于支持开发组合速释控释制剂的情况。
讨论了使用 PBPK 建模的未来展望，特别关注将体外溶解数据整合到用于口服和非口服给予药物的 PBPK 模型中。
