ADME/Permeability

 

ADMET Cartridge & Array HTAS Application

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The study of ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) profiles of drug candidates during pre-clinical development represents one of the major bottlenecks of the drug discovery process. In the current “fail early, fail fast” world of pharmaceutical development, High Throughput ADMET screening process will provide rapid and robust information necessary for critical “go or no go” decision making. Saving time required to make these decisions will potentially save the pharmaceutical industry money, make available more resources and will ultimately reduce the time to market for new drugs.

 

Recent advancements in Genomics, Proteomics, High-Throughput Screening (HTS) and the overall drug discovery process have rapidly generated large numbers of potential pharmacologically active compounds waiting for optimization and pre-clinical ADMET evaluation. In fact, similar bottlenecks exist in chemical, agricultural, cosmetic, and other industries involved in developing novel chemical entities and materials.

 

In the High Throughput ADMET screening process, the absorption study is considered the most limiting step because technology limits and difficulty in modeling in vivo environments. Current methods and instrumentation available for drug adsorption studies (e.g. everted sac, Ussing Chamber, cell culture and other in vitro techniques) have limited throughput or use cancerous cell lines with altered properties. Therefore they are unable to alleviate the backlog of drug candidates waiting for ADMET screening.

 

TechElan has focused its efforts on High Throughput ADMET and is pleased to present an automated High-Throughput ADMET System (HTAS). HTAS is designed to provide an automated assay system for high-throughput and high-content screening of permeability, absorption and other related ADMET parameters in environment resembling those in vivo. 

 

 Characteristics of the HTAS include:

 

bullet High throughput, multi-parallel design
bullet Efficient arrays of self-sealing, membrane chambers
bullet Utilization of live tissue and/or artificial membranes
bullet In vitro conditions closely matching those in vivo
bullet Availability of real time data and process kinetics
bullet Low cost of sample preparation
bullet Automated sample loading, testing and disposal
bullet Disposables sample holders
bullet Standardized investigative modules in multiples of 8 or 12
bullet Low cost of instrument operation and maintenance
bullet Reduced tissue sample size (material consumption)
bullet User friendly interface and data acquisition
bullet Small physical footprint of the system

 

A major effort was directed towards the development of a high-throughput ADMET (Adsorption, Distribution, Metabolism, Excretion and Toxicity) evaluation platform, which can address various ADMET parameters using either artificial membranes or live tissues in an automated high-throughput fashion. This ADMET platform is designed to accelerate pre-clinical toxicology screens to eventually match current high-throughput capabilities in the generation of lead compounds. Evaluation of this technology platform is currently being evaluated towards applications in cosmetics and nutraceuticals.

 

 Please see the following sections for more detailed information.