title: Predictive, non-GLP models of secondary pharmacodynamics: putting the best compounds forward.
abstract: Secondary pharmacodynamic studies of new chemical entities (NCEs) play a critical role in support of efficient drug discovery. In an era in which speed and efficiency are the norm for pharmaceutical discovery, the need to identify NCEs with greater patient tolerability continues to increase. Early use of secondary pharmacodynamic models (in vivo and in vitro) provides the foundation for critical, early decisions regarding lead molecules. Scientifically robust, non-GLP (good laboratory practices) secondary pharmacodynamic studies can eliminate compounds or structural series with undesirable profiles early, and may prove useful in defining structure-activity relationships (SARs) with regards to off-target effects.
authors.affiliation: Dept. R46R, Bldg. AP9, Abbott Laboratories, Abbott Park, IL 60064-6119, USA.
authors.forename: Glenn A
authors.initials: GA
authors.lastname: Reinhart
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Fryer
authors.forename: Mark A
authors.initials: MA
authors.lastname: Osinski
authors.forename: James S
authors.initials: JS
authors.lastname: Polakowski
authors.forename: Bryan F
authors.initials: BF
authors.lastname: Cox
authors.forename: Gary A
authors.initials: GA
authors.lastname: Gintant
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000187:drug effects; D004353:Drug Evaluation, Preclinical / Q000379:methods* / Q000592:standards*; D041981:Gastrointestinal Tract / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D023421:Models, Animal; D010599:Pharmacokinetics