Reasons for monitoring kinetics in safety evaluation studies.

Studies of the toxicity of a potential new drug form the basis of its preclinical safety evaluation and it is important that these toxicity studies are designed and conducted in a rational manner to permit the reliable interpretation and extrapolation of the resulting data to man. It is proposed that these objectives are more likely to be met with the support of pharmacokinetic data. Generally, toxicity studies include four groups of animals, a control group and three treated groups receiving low, intermediate and high dose levels respectively. In order to assist in the proper selection of appropriate dose levels and to increase the usefulness of the data obtained from toxicity studies, information on the following should be known. Relationship between dose level and the extent of absorption of the test compound. Effect of repeated (chronic) doses on the pharmacokinetics of the test compound. Relationship between the age of the animal and pharmacokinetics of the test compound. Relationship between the dose regimen used clinically and those used in toxicity studies.