ABSTRACT
In general, one can divide the applications of absorption, distribution, metabolism and excretion (ADME) data into three categories relative to toxicity evaluations: study design, interpretation and extrapolation. ADME data aid in the understanding of the animal model and often provide explanations or clues to unusual or unexpected results. This chapter determines whether the animal model is comparable to man in terms of chemical disposition and metabolism. Factors such as availability, economy of care and housing, uniformity, hardiness, regulatory guidelines, statistical power and historical experience, all have an impact on animal selection. It is useful to understand the relationship between the ‘effective dose’ and that which was administered to the test animals. Particularly important in laboratories where large numbers of test compounds are evaluated in ‘routine’ toxicity testing, is the need for reliable and predictable animal models that are well studied. At least from a pharmacokinetic standpoint, the rat is a reasonable laboratory animal model for extrapolation to man.
