Linear and nonlinear system approaches in pharmacokinetics: how much do they have to offer? II. The response mapping operator (RMO) approach.

The description of the relationship between different responses measured simultaneously in the same subject is commonly described in terms of specific pharmacokinetic models such as linear compartmental models. An alternative system approach involving response mapping operators (RMOs) is presented. The theoretical and mathematical basis of the RMO approach are derived. The assumptions, limitations, and practical significance of the RMO approach are discussed. The derivation of the RMO is illustrated with several examples. An algorithm and computer program for implementing the RMO in a routine manner is presented. The usage of the computer programs RMO and MAP presented are demonstrated using the pharmacokinetics of trimazosin and cefamandole in humans as examples. The RMO approach offers a new and powerful tool in pharmacokinetic analysis, which allows the investigator to approach certain problems in an objective, rational way without getting involved in specific pharmacokinetic modeling.