This contract provides a resource for preclinical pharmacology investigations of antitumor and anti-HIV agents under development by the Division of Cancer Treatment and Diagnosis, NCI. Defined pharmacological studies are assigned to the contractor through a Work Assignment system. These studies may include (1) development and validation of sensitive analytical methodology for quantitation of compounds in biological fluids and tissues; (2) in vitro stability and protein binding studies; (3) comparative in vitro metabolism studies using animal and human tissue preparations and expressed CYP450 isoforms; (4) determination of pharmacokinetic profiles and derived parameters following intravenous, intraperitoneal, subcutaneous (bolus and/or infusion) and oral dosing in rodents, dogs, and non-human primates; and (5) identification and pharmacokinetic analysis of drug metabolites. Data obtained in these studies are used to determine the most appropriate route, dose, and schedule of administration for achieving sustained therapeutic concentrations of an agent in biological fluids. For some compounds, particularly cytostatic antitumor or anti-HIV agents (which may be administered to patients for long periods of time), determination of oral bioavailability is emphasized. Preclinical pharmacology studies are generally performed in parallel with (and are designed to aid in the interpretation of) preclinical toxicology evaluations. Together, these investigations provide necessary data for IND filing as well as a rational basis for the clinical Phase I starting dose and dose escalation scheme.

Agency
National Institute of Health (NIH)
Institute
Division of Cancer Treatment (NCI)
Type
Research and Development Contracts (N01)
Project #
N01CM007111-000
Application #
6209007
Study Section
Project Start
1999-12-01
Project End
2004-11-30
Budget Start
1999-12-01
Budget End
2000-11-30
Support Year
Fiscal Year
2000
Total Cost
$64,963
Indirect Cost
Name
University of Alabama Birmingham
Department
Pharmacology
Type
Schools of Medicine
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294
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