This contract provides a resource for conducting preclinical pharmacology, pharmacokinetic, and metabolism studies with candidate therapeutic agents selected for development by the Division of Cancer Treatment, NCI. Most of the compounds selected are potential anticancer agents, but some are putative therapeutics for a wide range of prevalent and orphan human diseases. Compounds selected for study under this contract arise from peer-reviewed applications submitted to NCI by academic investigators, pharmaceutical companies, or others. Work carried out under the contract may include: (1) development of analytical methods to quantify compounds in plasma, urine, and other biological matrices;(2) plasma stability and protein binding studies;(3) pharmacokinetic characterization following administration to animals by various routes and schedules;(4) quantification and identification of drug metabolites generated in vivo and in various in vitro systems;and (5) assessment of pharmacodynamic effects in tumor or surrogate tissues and correlation of these effects with drug levels and/or total drug exposures. The characterizations obtained from these pharmacokinetic investigations will be used in the prioritization and selection of agents for further development;in the design of preclinical efficacy and toxicology studies;and in regulatory submissions in support of clinical trials of selected agents.
