Expert Opin Drug Metab Toxicol. 2011 Aug;7(8):929-34. doi: 10.1517/17425255.2011.585968.
The application of in silico methods for predicting internal dosimetry of a compound has gained attention in the past few years from academia, government and industry. One such method based on both compound- and organism-specific information is physiologically-based pharmacokinetic (PBPK) modeling. Numerous promises surrounding the potential of PBPK models to guide drug development (DD) and human health risk assessment (HHRA) have been made with primary areas of application being incorporation of in vitro data for pharmacokinetic prediction in early drug development, interspecies scaling, intra-human scaling and, of special interest, prediction of drug-drug interaction potential. This article addresses the question 'Have physiologically-based pharmacokinetic models delivered?' through analysis of its promises and accomplishments in real-world situations. Progress on PBPK model use in DD and HHRA has been demonstrated, especially in the area of interspecies and adult-to-children scaling, although its actual application is not reflected in the number of published works. Future advances will depend on continued model development as well as integration of PBPK models with models of response and/or disease. More importantly, increased training along with managerial and regulatory support is imperative to the continued integration of PBPK modeling in both HHRA and DD.
过去几年，学术界、政府和工业界都开始关注通过计算机模拟方法来预测化合物的体内剂量。基于化合物和生物体特定信息的生理相关药代动力学（PBPK）建模就是这样一种方法。人们对 PBPK 模型在药物开发（DD）和人类健康风险评估（HHRA）方面的潜在应用做出了诸多承诺，主要应用领域包括：将体外数据纳入早期药物开发的药代动力学预测，种间缩放，人体内缩放，以及特别关注的药物相互作用潜力预测。本文通过分析 PBPK 模型在实际情况下的承诺和成就，探讨了“生理相关药代动力学模型是否已经实现？”这一问题。DD 和 HHRA 中 PBPK 模型的使用取得了进展，尤其是在种间和成人到儿童缩放方面，尽管其实际应用并未反映在发表的作品数量上。未来的进展将取决于模型的持续开发，以及将 PBPK 模型与反应和/或疾病模型的整合。更重要的是，为了在 HHRA 和 DD 中继续整合 PBPK 建模，必须增加培训以及管理和监管支持。
