title: Tissue bioanalysis of biotherapeutics and drug targets to support PK/PD.
abstract: Contemporary drug discovery leverages quantitative modeling and simulation with increasing emphasis, both to gain deeper knowledge of drug targets and mechanisms as well as improve predictions between preclinical models and clinical applications, such as first-in-human dose projections. Proliferation of novel biotherapeutic modalities increases the need for applied PK/PD modeling as a quantitative tool to advance new therapies. Of particular relevance is the understanding of exposure, target binding and associated pharmacology at the target site of interest. Bioanalytical methods are key to informing PK/PD models and require assessment of both PK and PD end points. Where targets are sequestered in tissues (noncirculating), the ability to quantitatively measure drug or biomarker in tissue compartments becomes particularly important. This perspective provides an overview of contemporary applications of quantitative bioanalysis in tissue compartments as applied to PK and PD assessments associated with novel biotherapeutics. Case studies and key references are provided.
authors.affiliation: Pharmacokinetics Dynamics & Metabolism, Pfizer Inc., 1 Burtt Road, Andover, MA 01810, USA. hendrik.neubert@pfizer.com
authors.forename: Hendrik
authors.initials: H
authors.lastname: Neubert
authors.forename: Scott
authors.initials: S
authors.lastname: Fountain
authors.forename: Lindsay
authors.initials: L
authors.lastname: King
authors.forename: Tracey
authors.initials: T
authors.lastname: Clark
authors.forename: Yan
authors.initials: Y
authors.lastname: Weng
authors.forename: Denise M
authors.initials: DM
authors.lastname: O'Hara
authors.forename: Wenlin
authors.initials: W
authors.lastname: Li
authors.forename: Sheldon
authors.initials: S
authors.lastname: Leung
authors.forename: Chad
authors.initials: C
authors.lastname: Ray
authors.forename: Joe
authors.initials: J
authors.lastname: Palandra
authors.forename: Mireia Fernández
authors.initials: MF
authors.lastname: Ocaña
authors.forename: Jianqing
authors.initials: J
authors.lastname: Chen
authors.forename: Chengjie
authors.initials: C
authors.lastname: Ji
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Wang
authors.forename: Kimberly
authors.initials: K
authors.lastname: Long
authors.forename: Boris
authors.initials: B
authors.lastname: Gorovits
authors.forename: Eric
authors.initials: E
authors.lastname: Fluhler
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001702:Biopharmaceutics; D002623:Chemistry Techniques, Analytical; D006801:Humans; D004364:Pharmaceutical Preparations / Q000032:analysis*
chemical_list: D015415:Biomarkers; D004364:Pharmaceutical Preparations