Preclinical ADME/Tox & Rodent Efficacy

Preclinical studies are the link between the laboratory development of candidate compounds and the initiation of human clinical trials. Lead compounds whose activity has been optimized in in vitro systems are advanced to the preclinical research stage where the pharmacokinetics (PK), pharmacodynamics, in vivo efficacy and general safety profile are delineated. At this stage an in vivo ADME/Tox profile is generated and the list of potential clinical candidates is further narrowed. The PK data are also used to guide formulations to maximize compound exposure in vivo, to set the initial starting doses, and to determine the route of administration for clinical trials. Through collaboration with the Department of Pharmaceutical Sciences, the UPDDI has access to preclinical in vivo testing facilities for studying compound metabolism, pharmacokinetics, in vivo efficacy and non-GLP toxicology studies in rodent models. Capabilities include range-finding toxicology studies for determining maximum tolerated dose and to guide PK and efficacy studies, and analytical methods development to determine the concentrations of the compound and potential metabolites in tissues and excreta in order to determine the elimination routes of compounds and their metabolites. In addition, in vivo efficacy studies can also be set up to identify which candidates have the desired activity in an intact physiological system. Data from these preclinical studies feed back to the project teams to guide further optimization of lead compound series and enable rational decisions to be made on advancing compounds further in the drug discovery pipeline.