ASSESSING DRUG EXPOSURE IN RODENT TOXICITY STUDIES WITHOUT SATELLITE ANIMALS

Five major objectives for pharmacokinetic investigations in support of toxicity studies are identified as follows: Assess whether animals exhibited measurable blood concentrations in a dose-dependent manner; estimate average area under the concentration-time curve (AUC) and maximal concentration (C(max)) for each treatment group; elucidate general patterns in the concentration-time (CxT) profile, and summarize relationships between CxT and treatment group; determine CxT dependence on day into study; and judge interanimal variabilitly and identify any animals with unusual concentration response. Such objectives are generally addressed in rodent toxicity studies by including ''satellite'' animals in the study. Satellite animals are extra animals dosed as per protocol but not subjected to toxicological and pathological observations and tests. Instead, they are used exclusively for the evaluation of pharmacokinetic characteristics of the test compound. In this paper, methods are described for achieving the five listed pharmacokinetic objectives in rodent toxicity studies without the use of satellite animals. A rat toxicity study is presented as an example.