What Use is Toxicokinetics?

Abstract

The two principal goals of a drug development program for man or animals are to demonstrate efficacy and toxicity in such a way that the relative benefit and risk of therapy can be assessed, as that judgment will determine the success or failure of the treatment. Within this paradigm, the role of the preclinical phase is to explore the nature and mechanism of the desired activity and of any adverse effects in appropriate animal and in vitro models, so that the probable clinical value and precautions can be indicated as a guide to subsequent therapeutic trials. The latter are the definitive test of efficacy and harm, whether in all patients or in special subgroups. As the preclinical and clinical phases overlap, and more importantly because one of the purposes of focused nonclinical studies is to explore mechanisms in ways that are possible in patients, there is always a good deal of two-way transfer of information between the various phases, with findings in one being used as the basis for investigation and confirmation in the other.

Toxicokinetics forms an essential part of the initial toxicity tests done to screen for possible adverse effects; it is a vital component of studies in healthy volunteers and patients, and it is usually much involved in planning and interpreting specific experiments done to explore the causes and nature of desired and adverse effects. In essence, the regulation of medicines follows the same processes and asks the same questions, but it may appear to view the answers in a different way, by making a dispassionate analysis of the strength of the cases for and against the drug under circumstances in which both the generality and the strength of the evidence are tested, and weaknesses and omissions are probed in the attempt to define the quality and strength of the evidence for benefit and harm.