Extrapolation from animals to man. The integration of pharmacokinetics and pharmacodynamics

This paper has focused on the difficulties of extrapolating toxicological or pharmacological data obtained from animals to those expected in man. For some drugs, under certain conditions, there may be no problem, but for many, this is clearly not the case. Differences in apparent activity are impossible to reconcile without "normalizing" the dose for differences in pharmacokinetics and metabolism. The increasing use of artificial intelligence and expert systems in drug investigations may provide a greater insight into why these differences may occur and allow prediction but, in the end, they must be tested in the experiments undertaken. The use of kinetic dynamic relationships in different species will certainly help in this regard and, wherever possible, should be included in experimental design to build up a database of experience since such information is sadly lacking. But we must interpret with caution the data produced by those that continue to extrapolate animal data to humans without some attempt to discuss in detail the validity of their assumptions.