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

被引：61

作者：

Hop, Cornelis E. C. A. ^{[1
]}

Cole, Mark J. ^{[1
]}

Davidson, Ralph E. ^{[1
]}

Duignan, David B. ^{[1
]}

Federico, James ^{[1
]}

Janiszewski, John S. ^{[1
]}

Jenkins, Kelly ^{[1
]}

Krueger, Suzanne ^{[1
]}

Lebowitz, Rebecca ^{[1
]}

Liston, Theodore E. ^{[1
]}

Mitchell, Walter ^{[1
]}

Snyder, Mark ^{[1
]}

Steyn, Stefan J. ^{[1
]}

Soglia, John R. ^{[1
]}

Taylor, Christine ^{[1
]}

Troutman, Matt D. ^{[1
]}

Umland, John ^{[1
]}

West, Michael ^{[1
]}

Whalen, Kevin M. ^{[1
]}

Zelesky, Veronica ^{[1
]}

Zhao, Sabrina X. ^{[1
]}

机构：

[1] Pfizer Global Res & Dev, Groton, CT 06340 USA

来源：

CURRENT DRUG METABOLISM | 2008年 / 9卷 / 09期

关键词：

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

D O I：

10.2174/138920008786485092

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：847 / 853

页数：7

共 36 条

[31] Ultra-performance liquid chromatography/tandem mass spectrometric determination of testosterone and its metabolites in in vitro samples [J].