High throughput ADME screening: practical considerations, impact on the portfolio and enabler of in silico ADME models.
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.
Hop
Cornelis E C A
CE
Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA. hop.cornelis@gene.com
Cole
Mark J
MJ
Davidson
Ralph E
RE
Duignan
David B
DB
Federico
James
J
Janiszewski
John S
JS
Jenkins
Kelly
K
Krueger
Suzanne
S
Lebowitz
Rebecca
R
Liston
Theodore E
TE
Mitchell
Walter
W
Snyder
Mark
M
Steyn
Stefan J
SJ
Soglia
John R
JR
Taylor
Christine
C
Troutman
Matt D
MD
Umland
John
J
West
Michael
M
Whalen
Kevin M
KM
Zelesky
Veronica
V
Zhao
Sabrina X
SX
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
D004364:Pharmaceutical Preparations