The aim of the proposed research is to develop tools for the prediction of the distribution of drug compounds in the human body. There is currently no experimental high throughput screening (HTS) method for determining compound tissue distribution. A drug compound's propensity to be taken up by different tissues and organs affects whether it will reach its action target, whether it will cause undesirable side-effects and hence, whether it will be clinically viable. A high-throughput in vitro method for predicting distribution of drug compounds in the human body would be an important addition to pre-clinical screening of new chemical entities (NCEs). This proposal is for the development of a novel method for the prediction for NCEs of the overall volume of distribution (Vss) and the relative distribution among tissues, consisting of a unique combination of simple fluorescent liposome-based in vitro screening assays and state- of-the-art computational models. The proposed method will be used in the pre-clinical evaluation of drug candidates to provide a standard and cost effective way to predict the overall distribution and specific tissue uptake of drug candidates. Prediction of what will happen to a drug compound in the body is an important part of the drug development process. We are proposing to develop new tools for predicting where in the human body drug compounds will be distributed; this information will allow drug developers to determine early in the development cycle whether their drug candidates will reach their target and aid in their analysis of overall compound pharmacokinetics. Implementation of these tools will reduce the cost of drug development and accelerate the drug discovery process.
Thesaurus Terms: adipose tissue, bioassay, drug metabolism, high throughput technology, method development, protein localization biomimetics, computational biology, drug screening /evaluation, liposome, pharmacokinetics, plasma, tissue fluorescent dye /probe
