• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of pharmacokinetics and biopharmaceutics >Lumping of whole-body physiologically based pharmacokinetic models.
【24h】

Lumping of whole-body physiologically based pharmacokinetic models.

机译：基于全身生理学的药代动力学模型的集总。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Lumping is a common pragmatic approach aimed at the reduction of whole-body physiologically based pharmacokinetic (PBPK) model dimensionality and complexity. Incorrect lumping is equivalent to model misspecification with all the negative consequences to the subsequent model implementation. Proper lumping should guarantee that no useful information about the kinetics of the underlying processes is lost. To enforce this guarantee, formal standard lumping procedures and techniques need to be defined and implemented. This study examines the lumping process from a system theory point of view, which provides a formal basis for the derivation of principles and standard procedures of lumping. The lumping principle in PBPK modeling is defined as follows: Only tissues with identical model specification, and occupying identical positions in the system structure should be lumped together at each lumping iteration. In order to lump together parallel tissues, they should have similar or close time constants. In order to lump together serial tissues, they should equilibrate very rapidly with one another. The lumping procedure should include the following stages: (i) tissue specification conversion (when tissues with different model specifications are to be lumped together); (ii) classification of the tissues into classes with significantly different kinetics, according to the basic principle of lumping above; (iii) calculation of the parameters of the lumped compartments; (iv) simulation of the lumped system; (v) lumping of the experimental data; and (vi) verification of the lumped model. The use of the lumping principles and procedures to be adopted is illustrated with an example of a commonly implemented whole-body physiologically based pharmacokinetic model structure to characterize the pharmacokinetics of a homologous series of barbiturates in the rat.
机译：集总是一种通用的实用方法，旨在降低全身生理学上的药代动力学（PBPK）模型的尺寸和复杂性。不正确的集总等效于模型错误指定，对后续模型实现产生所有负面影响。适当的集总区应该确保不会丢失有关基础过程动力学的有用信息。为了执行此保证，需要定义和实施正式的标准集总程序和技术。这项研究从系统理论的角度检查了集总过程，这为集总的原理和标准程序的推导提供了正式的基础。 PBPK建模中的集总原理定义如下：在每次集总迭代时，只有具有相同模型规格且在系统结构中占据相同位置的组织才应集总在一起。为了将平行组织聚集在一起，它们应具有相似或接近的时间常数。为了使连续的组织聚集在一起，它们应该非常迅速地相互平衡。集总程序应包括以下阶段：（i）组织规格转换（将具有不同型号规格的组织集中在一起时）; （ii）根据上述基本原理将组织分为动力学明显不同的类别; （iii）计算集总隔室的参数; （iv）集总系统的仿真; （v）汇总实验数据; （vi）验证集总模型。以普遍采用的基于全身生理学的药代动力学模型结构为例来说明将要采用的集总原则和程序的使用，以表征大鼠中巴比妥类药物的同源系列的药代动力学。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号