What is available A broad range of tasks are available for assessing the safety and/or pharmacokinetics of each ligand. Specific capabilities available to investigators include:

• Validation of the analytical methods for quantitating drug concentrations in dosing solutions, biological fluids, and tissues, as required. Determination of plasma drug levels in animals administered the agent under study, and calculation of pharmacokinetic parameters derived from these data.
• Determination of bioavailability of the drug after different routes of administration, including oral, intravenous (i.v.), subcutaneous (s.c.), intramuscular (i.m.), or intraperitoneal (i.p.), as needed. Calculation of the pharmacokinetic parameters from the derived data.
• In vitro evaluation of hepatotoxicity in human and animal liver cells.
• Preclinical acute toxicity evaluations on lead compounds, evaluating clinical observations, body weights, clinical pathology, histopathology, and plasma drug levels in rodents and non-rodent species. Other toxicology endpoints may be selected if needed.
• Subacute and subchronic toxicity evaluations in rodents and large animal species, evaluating clinical observations, body weights, clinical pathology, and histopathology.
• Genotoxicity assessments using a battery of appropriate assays.

Since these preclinical studies are needed to demonstrate to the FDA that a candidate medication or imaging agent is understood well enough for designing appropriate clinical treatment regimens, most of the work to be conducted to achieve these objectives must be performed and the resulting data analyzed and reported in strict compliance with the FDA’s GLP regulations for nonclinical laboratory studies (21 CFR 58). These data must be obtained by carefully planned and skillfully executed methods that are specific, accurate, and precise. The applicable portions of the accumulated safety data will be included in documents submitted to the FDA in support of regulatory applications.

Who is eligible