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

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.