J
JianHua Liu
Researcher at Pfizer
Publications - 11
Citations - 918
JianHua Liu is an academic researcher from Pfizer. The author has contributed to research in topics: Potentiator & AMPA receptor. The author has an hindex of 8, co-authored 11 publications receiving 848 citations.
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Journal ArticleDOI
The impact of p-glycoprotein on the disposition of drugs targeted for indications of the central nervous system: evaluation using the mdr1a/ 1b knockout mouse model
Angela C. Doran,R. Scott Obach,Bill J. Smith,Natilie Hosea,Stacey L. Becker,Ernesto Callegari,Cuiping Chen,Xi Chen,Edna F. Choo,Julie Cianfrogna,Loretta M. Cox,John P. Gibbs,Megan A. Gibbs,Heather L. Hatch,Cornelis E. C. A. Hop,Ilana N. Kasman,Jennifer L. LaPerle,JianHua Liu,Xingrong Liu,Michael J. Logman,Debra Maclin,Frank M. Nedza,Frederick R. Nelson,Emily R. Olson,Sandhya Rahematpura,David Raunig,Sabrinia Rogers,Kari Schmidt,Douglas K. Spracklin,Mark A. Szewc,Matthew D. Troutman,Elaine E. Tseng,Meihua Tu,Jeffrey Van Deusen,Karthik Venkatakrishnan,Gary Walens,Ellen Q. Wang,Diane Wong,Adam Yasgar,Chenghong Zhang +39 more
TL;DR: It appears that most CNS-active agents demonstrate at least some P-gp-mediated transport that can affect brain concentrations, and unbound plasma concentrations may need to be greater than values projected using receptor affinity data to achieve adequate receptor occupancy for effect.
Journal ArticleDOI
Use of a Physiologically Based Pharmacokinetic Model to Study the Time to Reach Brain Equilibrium: An Experimental Analysis of the Role of Blood-Brain Barrier Permeability, Plasma Protein Binding, and Brain Tissue Binding
Xingrong Liu,Bill J. Smith,Cuiping Chen,Ernesto Callegari,Stacey L. Becker,Xi Chen,Julie Cianfrogna,Angela C. Doran,Shawn D. Doran,John P. Gibbs,Natilie Hosea,JianHua Liu,Frederick R. Nelson,Mark A. Szewc,Jeffery Van Deusen +14 more
TL;DR: The present study demonstrates that rapid brain equilibration requires a combination of high BBB permeability and low brain tissue binding, and the strategy to select compounds with rapid brain Equilibration in drug discovery should identify compounds with highBBB permeable and low nonspecific binding in brain tissue.
Journal ArticleDOI
Evaluation of cerebrospinal fluid concentration and plasma free concentration as a surrogate measurement for brain free concentration.
Xingrong Liu,Bill J. Smith,Cuiping Chen,Ernesto Callegari,Stacey L. Becker,Xi Chen,Julie Cianfrogna,Angela C. Doran,Shawn D. Doran,John P. Gibbs,Natilie Hosea,JianHua Liu,Frederick R. Nelson,Mark A. Szewc,Jeffrey Van Deusen +14 more
TL;DR: For quick brain penetration with simple diffusion mechanism compounds, CCSF and Cu,plasma represent Cu,brain equally well; for efflux substrates or slow brain penetration compounds,CCSF appears to be equivalent to or more accurate than Cu, Plasma to representCu,brain.
Journal ArticleDOI
Enhancing ketamine translational pharmacology via receptor occupancy normalization.
TL;DR: This work defines the NMDAR occupancy (RO) time course following single doses of ketamine in rats, nonhuman primates (nhp) and humans to allow direct interspecies comparisons of specific ketamine-mediated pharmacodynamics via RO normalization.
Journal ArticleDOI
Positive Allosteric Modulation of AMPA Receptors from Efficacy to Toxicity: The Interspecies Exposure-Response Continuum of the Novel Potentiator PF-4778574
Christopher L. Shaffer,Raymond S. Hurst,Renato J. Scialis,Sarah M. Osgood,Dianne K. Bryce,William E. Hoffmann,John T. Lazzaro,Ashley N. Hanks,Susan M. Lotarski,Mark L. Weber,JianHua Liu,Frank S. Menniti,Christopher J. Schmidt,Mihály Hajós +13 more
TL;DR: The resulting empirically derived exposure-response continuum for PF-4778574 defines a single-dose-based TI of 8- to 16-fold for self-limiting tremor, a readily monitorable clinical adverse event.