Recent Advances in Development and Application of Physiologically-Based Pharmacokinetic (PBPK) Models: a Transition from Academic Curiosity to Regulatory Acceptance
Recent Advances in Development and Application of Physiologically-Based Pharmacokinetic (PBPK) Models: a Transition from Academic Curiosity to Regulatory Acceptance
复制标题
基于生理学的药代动力学（PBPK）模型的开发和应用的最新进展：从学术好奇心到监管接受的转变
作者：
M. Jamei
制药行业和监管机构对基于生理学的药代动力学 (PBPK) 模型的应用重新产生了兴趣。在系统药理学背景下开发 PBPK 模型可以将与动物或人体（系统）有关的参数与药物和研究设计的参数分开，这对于开发用于推断各种健康和患者群体中 PK/PD 特性的通用药物独立模型至关重要。这将经典范式扩展为“预测-学习-确认-应用”概念。最近，许多药物标签都通过使用 PBPK 模型生成的模拟结果来获取信息。这些案例表明，要么使用模拟来代替进行临床研究，要么已经告知药物标签，否则在某些特定情况下药物标签会保持沉默。在不久的将来，看到这些模型在护理点实施精确剂量的应用也就不足为奇了。
There is a renewed surge of interest in applications of physiologically-based pharmacokinetic (PBPK) models by the pharmaceutical industry and regulatory agencies. Developing PBPK models within a systems pharmacology context allows separation of the parameters pertaining to the animal or human body (the system) from that of the drug and the study design which is essential to develop generic drug-independent models used to extrapolate PK/PD properties in various healthy and patient populations. This has expanded the classical paradigm to a ‘predict-learn-confirm-apply’ concept. Recently, a number of drug labels are informed by simulation results generated using PBPK models. These cases show that either the simulations are used in lieu of conducting clinical studies or have informed the drug label that otherwise would have been silent in some specific situations. It will not be surprising to see applications of these models in implementing precision dosing at the point of care in the near future.