Department of Pharmaceutical Sciences, University at Buffalo, Buffalo, NY, USA.
J Pharmacokinet Pharmacodyn. 2012 Feb;39(1):109-23. doi: 10.1007/s10928-011-9236-y. Epub 2012 Jan 3.
In the field of hematology, several mechanism-based pharmacokinetic-pharmacodynamic models have been developed to understand the dynamics of several blood cell populations under different clinical conditions while accounting for the essential underlying principles of pharmacology, physiology and pathology. In general, a population of blood cells is basically controlled by two processes: the cell production and cell loss. The assumption that each cell exits the population when its lifespan expires implies that the cell loss rate is equal to the cell production rate delayed by the lifespan and justifies the use of delayed differential equations for compartmental modeling. This review is focused on lifespan models based on delayed differential equations and presents the structure and properties of the basic lifespan indirect response (LIDR) models for drugs affecting cell production or cell lifespan distribution. The LIDR models for drugs affecting the precursor cell production or decreasing the precursor cell population are also presented and their properties are discussed. The interpretation of transit compartment models as LIDR models is reviewed as the basis for introducing a new LIDR for drugs affecting the cell lifespan distribution. Finally, the applications and limitations of the LIDR models are discussed.
在血液学领域，已经开发了几种基于机制的药代动力学-药效动力学模型，以了解在不同临床情况下几种血细胞群体的动态变化，同时考虑药理学、生理学和病理学的基本原理。一般来说，血细胞群体主要受两个过程控制：细胞生成和细胞损失。当细胞寿命结束时，每个细胞离开群体的假设意味着细胞损失率等于寿命延迟的细胞生成率，这证明了使用时滞微分方程进行房室模型化是合理的。这篇综述重点介绍基于时滞微分方程的寿命模型，并介绍影响细胞生成或细胞寿命分布的药物的基本寿命间接反应（LIDR）模型的结构和性质。还介绍了影响前体细胞生成或减少前体细胞群体的药物的 LIDR 模型，并讨论了它们的性质。作为引入影响细胞寿命分布的药物的新 LIDR 的基础，回顾了传递室模型作为 LIDR 模型的解释。最后，讨论了 LIDR 模型的应用和局限性。
