G. GIORGI

P. BLARDI

R. URSO

Phamacokinetics is proposed to study the absorption, the distribution, the biotransformations and the elimination of drugs in man and animals. A single kinetic profile may be well summarized by Cmax, Tmax, t1/2 and AUC and, having more than one profile, 8 parameters at least, the mean and standard deviation of these parameters, may well summarize the drug kinetics in the whole population. A more carefull description of the data can be obtained interpolating and extrapolating the drug concentrations with some mathematical functions. These functions may be used to reduce all the data in a small set of parameters, or to verify if the hypotheses incorporated in the functions are confirmed by the observations. In the first case, we can say that the task is to get a simulation of the data, in the second to get a model. The functions used to interpolate and reduce the pharmacokinetic data are the multiexponential functions and the reference models are the compartmental models whose solutions are just the multiexponential functions. Using models, new meaningfull pharmacokinetic parameters may be defined which can be used to find relationships between the drug kinetic profile and the physiological process which drive the drug absorption, distribution and elimination. For example, compartmental models allow to define easily the clearance which is dependent on the drug elimination process, or the volume of distribution which depends on the drug distribution in the tissues. Models provide also an easy way to get an estimate of drug absorption after extravasculare drug administration (bioavailability). Model building is a complex multistep process where, experiment by experiment and simulation by simulation, new hypothesis are proven and disproven through a continuous interaction between the experimenter and the computer

A short introduction to pharmacokinetics.

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