Linear and nonlinear system approaches in pharmacokinetics: how much do they have to offer? I. General considerations.

System approaches in pharmacokinetics are defined as generalizing and simplifying modeling approaches that mathematically model a general property of the pharmacokinetic system without modeling specifically the individual kinetic processes responsible for the general property considered. The rationale for the use of system approaches is discussed and the kinetic basis of some of the approaches is presented. An overview of the approaches is presented together with a comparison to classical approaches involving specific pharmacokinetic models. Examples are given from different application areas involving problems in linear and nonlinear pharmacokinetics and in pharmacodynamics. The advantages, disadvantages, and limitations of the system approaches are discussed. In several application areas the system approach offers some rational methods and procedures with distinct advantages over more traditional approaches.