title: High throughput ADME screening: practical considerations, impact on the portfolio and enabler of in silico ADME models.
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.
authors.affiliation: Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA. hop.cornelis@gene.com
authors.forename: Cornelis E C A
authors.initials: CE
authors.lastname: Hop
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Cole
authors.forename: Ralph E
authors.initials: RE
authors.lastname: Davidson
authors.forename: David B
authors.initials: DB
authors.lastname: Duignan
authors.forename: James
authors.initials: J
authors.lastname: Federico
authors.forename: John S
authors.initials: JS
authors.lastname: Janiszewski
authors.forename: Kelly
authors.initials: K
authors.lastname: Jenkins
authors.forename: Suzanne
authors.initials: S
authors.lastname: Krueger
authors.forename: Rebecca
authors.initials: R
authors.lastname: Lebowitz
authors.forename: Theodore E
authors.initials: TE
authors.lastname: Liston
authors.forename: Walter
authors.initials: W
authors.lastname: Mitchell
authors.forename: Mark
authors.initials: M
authors.lastname: Snyder
authors.forename: Stefan J
authors.initials: SJ
authors.lastname: Steyn
authors.forename: John R
authors.initials: JR
authors.lastname: Soglia
authors.forename: Christine
authors.initials: C
authors.lastname: Taylor
authors.forename: Matt D
authors.initials: MD
authors.lastname: Troutman
authors.forename: John
authors.initials: J
authors.lastname: Umland
authors.forename: Michael
authors.initials: M
authors.lastname: West
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Whalen
authors.forename: Veronica
authors.initials: V
authors.lastname: Zelesky
authors.forename: Sabrina X
authors.initials: SX
authors.lastname: Zhao
mesh_terms: D000818:Animals; D003198:Computer Simulation; D004353:Drug Evaluation, Preclinical / Q000592:standards* / Q000706:statistics & numerical data; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010599:Pharmacokinetics; D011786:Quality Control
chemical_list: D004364:Pharmaceutical Preparations