Preclinical drug metabolism in the age of high-throughput screening: an industrial perspective.
With the advent of genomics, combinatorial paradigms and high-throughput screen (HTS)-based pharmacological testing, the number of compounds flowing through the discovery pipeline is likely to escalate. At the same time, with increased knowledge of the human drug-metabolizing enzymes and the availability of in vitro absorption-metabolism (AM) models, Preclinical Drug Metabolism is poised to meet the challenges of HTS. In order to be successful, however, a rational HTS strategy (vs. serendipitous HTS) has to be employed. Such a strategy is based on automation, validation and integration of in vitro AM models and database management (AVID). A generalized strategy for rational (AVID-based) HTS in Preclinical Drug Metabolism is described briefly.
Rodrigues
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Merck Research Laboratories, West Point, Pennsylvania 19486-0004, USA.
D000818:Animals; D016503:Drug Delivery Systems / Q000639:trends*; D004353:Drug Evaluation, Preclinical / Q000639:trends*; D004345:Drug Industry / Q000639:trends*; D006801:Humans; D010599:Pharmacokinetics