title: In vivo rat PK profiling in drug discovery: new challenges.
abstract: The importance of evaluating drug metabolism and pharmacokinetic (DMPK) properties very early in the drug discovery process in order to reduce attrition during development is now well recognised. In this paper we illustrate an approach for PK screening that provides a range of parameters that would not be available from conventional PK profiling. In combination with an assessment of physicochemical and in vitro properties, the in vivo PK protocol described provides better mechanistic understanding of the PK behaviour of a compound or class of compounds. The higher level of interpretation and use of in vitro and in vivo data better describe the disposition properties and give an estimation of the biophase concentration of the drug, providing a clear guidance for the design of higher quality molecules. Moreover, the collection of a broader set of in vivo and in vitro PK data improves the predictability of the DMPK science and it can allow an integrated safety risk assessment.
authors: GlaxoSmithKline SpA, Neurosciences Centre of Excellence for Drug Discovery, Medicine Research Centre, Verona, Italy.
authors: Laura
authors: L
authors: Zonzini
authors: Federica
authors: F
authors: Bianchi
authors: Nicola
authors: N
authors: Cesari
authors: Matteo
authors: M
authors: Sartori
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery / Q000379:methods*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007275:Injections, Intravenous; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism*; D010599:Pharmacokinetics; D051381:Rats / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D004364:Pharmaceutical Preparations