Centre for Applied Pharmacokinetics Research, School of Pharmacy and Pharmaceutical Sciences, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.
Clin Pharmacol Ther. 2012 Jul;92(1):50-61. doi: 10.1038/clpt.2012.65. Epub 2012 May 30.
Classic pharmacokinetics (PK) rarely takes into account the full knowledge of physiology and biology of the human body. However, physiologically based PK (PBPK) is built mainly from drug-independent "system" information. PBPK is not a new concept, but it has shown a very rapid rise in recent years. This has been attributed to a greater connectivity to in vitro-in vivo extrapolation (IVIVE) techniques for predicting drug absorption, distribution, metabolism, and excretion (ADME) and their variability in humans. The marriage between PBPK and IVIVE under the overarching umbrella of "systems biology" has removed many constraints related to cutoff approaches on prediction of ADME. PBPK-IVIVE linked models have repeatedly shown their value in guiding decisions when predicting the effects of intrinsic and extrinsic factors on PK of drugs. A review of the achievements and shortcomings of the models might suggest better strategies in extending the success of PBPK-IVIVE to pharmacodynamics (PD) and drug safety.
经典药代动力学（PK）很少考虑到人体生理学和生物学的全部知识。然而，基于生理学的 PK（PBPK）主要是基于与药物无关的“系统”信息构建的。PBPK 并不是一个新概念，但近年来它的发展非常迅速。这归因于与体外-体内外推（IVIVE）技术的更大连接，用于预测药物吸收、分布、代谢和排泄（ADME）及其在人体内的变异性。PBPK 与 IVIVE 在“系统生物学”的总体框架下的结合，消除了与 ADME 预测相关的许多基于截止值的方法的限制。PBPK-IVIVE 相关模型在指导预测内在和外在因素对药物 PK 的影响时，反复显示了它们的价值。对这些模型的成就和不足进行回顾，可能会为将 PBPK-IVIVE 在药效学（PD）和药物安全性方面的成功扩展提供更好的策略。
