Abstract
This presentation will discuss primary factors to address in determining exposure and dosing regimens, as well as exposure durations, in planning developmental neurotoxicity investigations. Whether the investigator employs a single dose during pregnancy, or continuous dosing prior to and throughout pregnancy (as well as during early postnatal development), the following primary factors should be addressed: 1) Purpose of the study (e.g., descriptive [such as screening] or investigative [such as determining the mechanism of action]); 2) physicochemical properties of the test compound that affect its pharmacokinetics and pharmacodynamics; 3) ability of the test compound to induce or inhibit metabolic enzymes; 4) appropriateness and characteristics of the test species; 5) limiting factors, including the availability of test compound for evaluation (e.g ., small quantities of a newly synthesized drug); and, 6) a number of general, miscellaneous factors (e.g., complications of maternal or fetal toxicity from extended dosing durations). Selection of exposure and dosing regimen (s), and exposure durations, most appropriate for a particular developmental neurotoxicity assessment requires careful attention to these factors.
