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High Throughput ADME Screening: Practical Considerations, Impact on the Portfolio and Enabler of In Silico ADME Models

[ Vol. 9 , Issue. 9 ]

Author(s):

Cornelis E.C.A. Hop, Mark J. Cole, Ralph E. Davidson, David B. Duignan, James Federico, John S. Janiszewski, Kelly Jenkins, Suzanne Krueger, Rebecca Lebowitz, Theodore E. Liston, Walter Mitchell, Mark Snyder, Stefan J. Steyn, John R. Soglia, Christine Taylor, Matt D. Troutman, John Umland, Michael West, Kevin M. Whalen, Veronica Zelesky and Sabrina X. Zhao   Pages 847 - 853 ( 7 )

Abstract:


Evaluation and optimization of drug metabolism and pharmacokinetic data plays an important role in drug discovery and development and several reliable in vitro ADME models are available. Recently higher throughput in vitro ADME screening facilities have been established in order to be able to evaluate an appreciable fraction of synthesized compounds. The ADME screening process can be dissected in five distinct steps: (1) plate management of compounds in need of in vitro ADME data, (2) optimization of the MS/MS method for the compounds, (3) in vitro ADME experiments and sample clean up, (4) collection and reduction of the raw LC-MS/MS data and (5) archival of the processed ADME data. All steps will be described in detail and the value of the data on drug discovery projects will be discussed as well. Finally, in vitro ADME screening can generate large quantities of data obtained under identical conditions to allow building of reliable in silico models.

Keywords:

Absorption, ADME, data management, in silico, in vitro, mass spectrometry, metabolism, pharmacokinetics

Affiliation:

Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.



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