Pharmacokinetics of endogenous substances: some problems and some solutions.

The paper deals with the most relevant aspects related to the pharmacokinetics of endogenous substances. Two different views are presented in order to focus on two aspects of the problem, the physiological background of these substances and the need for empirical or tailored models to process pharmacokinetic data. Very often endogenous substances follow saturable enzyme biotransformation, reversible interconversion, active and diffusional transports, renal threshold, endogenous synthesis plus dietary supply with possible balancement between these two factors, feedback processes, asymmetric distribution with specific body storage, and gender differences. These mechanisms allow the body to preserve and restore homeostatic equilibria of endogenous substances. The most relevant problem in pharmacokinetics of these substances is the presence of baseline concentration which needs to be carefully defined also for possible rhythms related to age, sex, diet, night and day periods. Theoretical considerations are presented for the management of pharmacokinetic analysis of these substances, which only rarely follow linear processes. Throughout the text various practical examples are considered.