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[描述药代动力学的模型及非模型方法:优点、缺点及相互关系]

[Model and model-independent methods of describing pharmacokinetics: the advantages, drawbacks and interrelationship].

作者信息

Piotrovskiĭ V K

出版信息

Antibiot Med Biotekhnol. 1987 Jul;32(7):492-7.

PMID:3674831
Abstract

A system for classification of the main quantitative approaches used in describing drug pharmacokinetics is proposed. The basis of the system is occupied by the systemic approach ignoring a detailed picture of the processes observed in the organism with participation of drugs and providing only integral description of such processes by parameters not depending on the concrete structure of the model. The second level is represented by stochastic models which also ignore the process detailed mechanism but provide concrete definition of the drug retention time frequency and distribution. The upper level is occupied by structural models (compartment and physiological) fixating a priori the concrete picture of the drug mass transfer in the organism which is more or less close to the real one. Interrelation of the three levels is analyzed. Definitions of the main model independent pharmacokinetic parameters such as total clearance, apparent volume distribution and mean retention time of the drug molecules in the organism are presented. A relationship between the drug concentration profile in blood and the drug retention time density distribution was developed. This relationship is the ground of the stochastic pharmacokinetic models.

摘要

提出了一种用于对描述药物药代动力学的主要定量方法进行分类的系统。该系统的基础是整体方法,它忽略了药物参与下在生物体中观察到的过程的详细情况,仅通过不依赖于模型具体结构的参数对这些过程进行整体描述。第二层由随机模型表示,随机模型同样忽略过程的详细机制,但提供药物保留时间频率和分布的具体定义。最高层由结构模型(房室模型和生理模型)占据,这些模型先验地确定生物体中药物质量传递的具体情况,且或多或少接近实际情况。分析了这三个层次的相互关系。给出了主要的与模型无关的药代动力学参数的定义,如总清除率、表观分布容积和药物分子在生物体中的平均保留时间。建立了血液中药物浓度曲线与药物保留时间密度分布之间的关系。这种关系是随机药代动力学模型的基础。

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