Model-free evaluation and mean-time concept in pharmacokinetics.

Pharmacokinetic characteristics may be separated into three classes: firstly, those which are truly independent of pharmacokinetic modelling - curve characteristics for instance, such as Cmax or tmax, but also organic clearance values; secondly, those which can be evaluated without an explicit pharmacokinetic model but under basic assumptions - characteristics such as total clearance, mean and variance of residence times or total volume of distribution; and thirdly, those which are bound to elaborate pharmacokinetic models, such as hybrid constants, micro-constants or partial volumes of distribution. It can be demonstrated that the second class - the model-independent evaluated characteristic - and the third are mutually transferrable; examples of this transcription are given. However, these purely theoretical considerations can only demonstrate that the second class is consistent with classic pharmacokinetic modelling. The usefulness of the model-independent evaluated characteristic is underlined by results of clinical pharmacological investigations in which this technique was applied. The topics addressed by these studies cover the problems of deep compartments, differences in absorption, influence of disease, drug interaction, and first-pass metabolization. Since the mean-time concept in particular is still controversial in the literature, some general theoretical explanations seem to be necessary.