The Utility of Semi-Automating Multiplexed Assays for ADME/Tox Applications

Brad      Larson; Peter      Banks; Sarah      Shultz; Mary      Sobol; James      J. Cali

Abstract

ADME-Tox testing examines the effects of an organism, tissue or cell on a compound, as well as the effects that the compound has on an organism, tissue or cell, and has gained in importance in the overall drug discovery process over the past twenty years. This is due to the rising percentage of drug candidate attrition in the 1990s and early 2000s due to adverse ADME/Tox profiles. The increased importance placed upon ADME/Tox testing has brought about new types of in-vitro assay technologies utilizing microplates to deliver the most pharmacologically relevant data. These tests, however, have typically been performed sequentially, where multiple assays over multiple microplates are used. This typically leads to increased time and cost required to generate the required information, and can sacrifice data quality. Multiplexed assays, however, where more than one piece of data can be attained from a single well or a single microplate, performed using appropriate liquid handling and detection instrumentation, can improve data quality and reduce the time and expense required to attain this information.

Keywords: ADME/Tox, apoptosis, automated profiling, cell viability, cytochrome p450, glucuronidation, luminescence, multiplexing, drug discovery process, pharmacokinetics, toxicity