In Vitro ADMET Laboratories Inc. obtains US Patent for the “Plated Hepatocyte Relay Assay” to Evaluate Slowly Metabolized Drugs

  COLUMBIA, MARYLAND - 01/17/2017 (PRESS RELEASE JET)

In Vitro ADMET Laboratories LLC (IVAL) is proud to announce that a U. S. Patent (US 9,518,979 B2;   Date of Patent: Dec. 13, 2016) has been allowed for its novel technology:  The Plated Hepatocyte Relay Assay (PHRA) for the evaluation of the metabolism of slowly metabolized chemicals.  This technology has been developed to overcome a current challenge in drug development, namely, the evaluation of the metabolic fate of drug candidates that are resistant to metabolism by current in vitro drug metabolism systems. 

The invention comprises sequential metabolism of a test compound for multiple days, with metabolism performed using cryopreserved hepatocytes freshly cultured on each day of evaluation as attached cells.  Due to the presence of active transporters and complete drug metabolizing enzymes and cofactors, hepatocytes are considered the “gold standard” for in vitro drug metabolism studies.  The use of attached rather than suspension hepatocyte cultures allows the extension of hepatocyte life span to over 24 hrs. The use of sequential metabolism using a new hepatocyte prepared daily overcomes the known culture-duration dependent decrease in hepatic metabolism capacity of cultured hepatocytes.  In this assay, cryopreserved human hepatocytes are cultured as attached cultures and incubated for 24 hours with the chemicals to be evaluated.  On the next day, the culture medium containing the parent chemical and the metabolites generated in the first 24 hours is transferred to a new freshly prepared culture of human hepatocytes for a second round of incubation (relay).  This process can be repeated at least 4 more times, allowing continuous incubation durations of 120 hours or more. 

“This is a major breakthrough in the application of in vitro experimental systems to understand the metabolic fate of drugs in human patients”, says Dr. Albert P. Li, Ph. D., President and C.E.O. of IVAL.  “In the early stages of drug development, in vitro experimental systems such as human liver microsomes or suspended human hepatocytes are routinely used to identify chemicals which are rapidly metabolized and eliminate them from further development.  As a result, drug candidates with high metabolic stability are being accumulated.  The current challenge in pharmaceutical industry is that the chemicals are nevertheless metabolized in vivo, while the routinely used in vitro systems such as human liver microsomes and suspended human hepatocytes would not be useful in the prediction of in vivo metabolism.  This invention, the “Plated Hepatocyte Relay Assay”, overcomes this challenge.  The assay allows continuous metabolism with human hepatocytes with physiologically relevant metabolic capacity for 5 days or more, allowing the elucidation of the metabolic fate of slowly metabolized chemicals in vivo – information that would allow the prediction of critical human clinical drug properties such as plasma half-life, pharmacological effects, drug-drug interaction potential, and toxicity”. 

The Plated Hepatocyte Relay Assay has been validated with model slowly-metabolized drugs to provide an accurate prediction of in vivo hepatic clearance.   Validation data can be found in the following publication:  Peng, C.C., Doshi, U., Prakash, C. and Li, A. P., 2016. A Novel Plated Hepatocyte Relay Assay (PHRA) for In Vitro Evaluation of Hepatic Metabolic Clearance of Slowly Metabolized Compounds. Drug metabolism letters, 10(1), pp.3-15.

In Vitro ADMET Laboratories Inc. is currently offering this assay as a contract research service.  This technology is also available for licensing for use by pharmaceutical companies and contract research laboratories.  Parties with interests in this novel technology can contact IVAL by telephone (+1-410-869-9037) or email (info@invitroadmet.com).

About In Vitro ADMET Laboratories LLC (IVAL).  IVAL was established by Dr. Albert P. Li in 2004.  Dr. Li is an internationally renowned expert of in vitro drug metabolism and toxicology.  The company manufactures research reagents and provides contract research services to aid drug discovery and drug development, focusing on in vitro evaluation of drug metabolism, drug-drug interactions, and drug toxicity.  IVAL is the world’s leading company in hepatocyte technologies, with widely-acclaimed hepatocyte products including high quality plateable cryopreserved human hepatocytes as well as plateable cryopreserved mouse, rat, dog, and monkey hepatocytes.  IVAL is located in Columbia, Maryland, and Malden, Massachusetts.  Further information concerning IVAL can be obtained at the company website:  www.invitroadmet.com or via contacting IVAL at info@invitroadmet.com.