HIGH-THROUGHPUT APPROACHES FOR EVALUATING ABSORPTION, DISTRIBUTION, METABOLISM AND EXCRETION PROPERTIES OF LEAD COMPOUNDS

Combinatorial chemistry methods and high-throughput screening for lead s in industrial drug discovery have generated a potential bottleneck i n the optimisation processes that seek to align potency with good phar macokinetics in order to produce good medicines. This has resulted in the need for higher throughput methods of screening for absorption, di stribution, metabolism and excretion properties. Significant progress has been made in throughput of in vivo pharmacokinetic studies, with t he introduction of cassette, or multiple-in-one, protocols. In this te chnique, typically up to ten compounds are administered in one dose an d analysed concomitantly on the mass spectrometer. High-throughput met hods in in vitro absorption, distribution, metabolism and excretion ar e less well-developed as yet, and current approaches comprise automati on of well-established methods for absorption using cell lines and met abolism using liver microsomes.