The objective of this contract is to acquire pharmacologic and toxicologic data on new drugs for the treatment of Cancer and the Acquired Immunodeficiency Syndrome (AIDS). The data will serve as the basis of the Government's filing for an INDA to institute human clinical trials. This data is collected in a series of toxicology and pharmacology studies and consists of the following: * Analytical Phase: Drug identity analysis (e.g., IR, NMR, MP, MS, etc.) validation of the procedures supplied by the NCI for dose concentration analyses and validation of the requisite methodology for assay of drug in biological fluids will be initiated immediately upon receipt of drug. * Pharmacokinetic Phase: Plasma elimination kinetics will be determined in dogs and possibly in rodents after single intravenous doses of drug. Bioavailability of non-parenteral routes and plasma clearance rates will be determined in order to establish the dose required to produce effective drug concentrations in plasma for future toxicity studies. The ability of an anti-AIDS drug to cross the blood-brain barrier will also be assessed in dogs and possibly rodents. * Preliminary Toxicity Phase: For each drug, it will be necessary to establish a maximum tolerated dose (MTD) and dose limiting toxicities (DLT) in both beagle dogs and rodents. * INDA-Directed Toxicity Phase: For each drug, it will be necessary to establish toxicity and safety in relation to drug plasma concentrations or area-under-the-curve in both beagle dogs and rodents. In the Preliminary Toxicity Phase and the INDA-Directed Toxicity Phase, the use of primates as an alternative species may be required on an infrequent basis.

Agency
National Institute of Health (NIH)
Institute
Division of Cancer Treatment (NCI)
Type
Research and Development Contracts (N01)
Project #
N01CM037835-006
Application #
2300656
Study Section
Project Start
1993-01-01
Project End
1995-10-31
Budget Start
1993-11-01
Budget End
1994-10-31
Support Year
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Southern Research Institute
Department
Type
DUNS #
006900526
City
Birmingham
State
AL
Country
United States
Zip Code
35205
Rodman, L E; Farnell, D R; Coyne, J M et al. (1997) Toxicity of cordycepin in combination with the adenosine deaminase inhibitor 2'-deoxycoformycin in beagle dogs. Toxicol Appl Pharmacol 147:39-45