Covance adopts unique in-vitro method to predict in-vivo liver disposition

The technique, B-CLEAR, has already demonstrated distinct characteristics in current proprietary absorption, distribution, metabolism, excretion and toxicology (ADMET) technologies. It gives scientists the ability to generate physiologically relevant data and enable decision making in pivotal areas related to hepatic transport and adverse drug interactions. Current drug R&D methods rely heavily on ADMET - a technique that incorporates a variety of methods such as animal models to predict the efficacy of a potential drug. Although popular, animal models have been used for many years and are still popular. However, due to differences within their physiology compared to humans, they don't always provide the most accurate results causing companies to look for more representative methods. In-silico​ modelling for ADMET is also becoming a popular method used for predictive toxicology. Normally, the use of in-silico​ modelling will be used in conjunction with other methods to determine compound characteristics. Covance intend to use B-CLEAR as an early discovery screen for promotion of compounds, a source of lead optimization guidance, and a tool to address development-stage drug transport questions, enabling better prediction of bioavailability, pharmacokinetics, species-specific drug dosing and candidate selection. "We're looking to B-CLEAR to help our customers identify and select better drug candidates,"​ said Jon Denissen Vice President of Chemistry, North America. "Adding B-CLEAR greatly compliments our existing strengths in metabolism and pharmacokinetic services that help drug researchers to improve candidate selection and progress drug candidates that have a higher chance for success."​ The B-CLEAR product line characterises compounds' hepatobiliary disposition (hepatic uptake, excretion and biliary clearance). Human (B-CLEAR-HU), monkey (B-CLEAR-MK), dog (B-CLEAR-DG), rat (B-CLEAR-RT), and mouse (B-CLEAR-MO) hepatocytes are available on the B-CLEAR system. According to Kalorama between forty and sixty per cent of lead compounds fail ADMET (absorption, distribution, metabolism, excretion and toxicology) testing, and only ten per cent of drugs that start clinical trials ever get approved. Overall, this means that seventy two per cent of drug development costs are wasted on failures. This has created a general theme in drug discovery to get much more information about drug compounds earlier in the process, to cut attrition rates by making compounds 'fail faster.' This involves much more use of computer modelling, high content screening and miniaturised assays, it notes.