Division 4.2.2 Pharmaco-kineticsF1

Pharmaco-kinetics means the study of the fate of the active substance, and its metabolites, within the organism, and covers the study of the absorption, distribution, metabolism (bio-transformation) and excretion of these substances.

The study of these different phases may be carried mainly by means of physical, chemical or possibly by biological methods, and by observation of the actual pharmaco-dynamic activity of the substance itself.

Information on distribution and elimination shall be necessary in all cases where such data are indispensable to determine the dosage for humans, and in respect of chemo-therapeutic substances (antibiotics, etc.) and substances whose use depends on their non-pharmaco-dynamic effects (e.g. numerous diagnostic agents, etc.).

In vitro studies also can be carried out with the advantage of using human material for comparison with animal material (i.e. protein binding, metabolism, drug-drug interaction).

Pharmaco-kinetic investigation of all pharmacologically active substances is necessary. In the case of new combinations of known substances, which have been investigated in accordance with the provisions of this Directive, pharmaco-kinetic studies may not be required, if the toxicity tests and therapeutic experimentation justify their omission.

The pharmaco-kinetic program shall be design to allow comparison and extrapolation between animal and human.