Abstract

The Pharmacokinetics/Pharmacodynamics Core (Core D) will provide analytic resources to each of the Projects in this application to measure concentrations of drugs and relevant biomarkers within various sample types. This will primarily be accomplished using a mass spectrometric approach, with which the principal investigator has significant expertise. Methods to detect drug and drug metabolites have already been developed for both the lead (P2176) and backup (P2114) compounds and successfully utilized to assess the pharmacokinetics of these drugs when applied to the airways. Similarly, methods to measure relevant biomarkers have been developed and yield biologically plausible results in preliminary experiments. Furthermore, the Core has the capability of adding new biomarkers as the need arises.

Public Health Relevance

The Pharmacokinetics/Pharmacodynamics Core (Core D) will provide the Projects in this application with the ability to measure concentrations and physiological effects of novel mucolytic drugs designed to treatment airways disease cystic fibrosis or asthma. These analyses will be available to all Projects within the proposal, as well as to the wider scientific community.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL108808-08
Application #
9780553
Study Section
Special Emphasis Panel (ZHL1)
Program Officer
Noel, Patricia
Project Start
Project End
Budget Start
2019-07-01
Budget End
2020-06-30
Support Year
8
Fiscal Year
2019
Total Cost
Indirect Cost

  Institution

Name
University of North Carolina Chapel Hill
Department
Type
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599

  Publications

Abdullah, Lubna H; Coakley, Raymond; Webster, Megan J et al. (2018) Mucin Production and Hydration Responses to Mucopurulent Materials in Normal versus Cystic Fibrosis Airway Epithelia. Am J Respir Crit Care Med 197:481-491
Yu, Dongfang; Saini, Yogesh; Chen, Gang et al. (2018) Loss of ? Epithelial Sodium Channel Function in Meibomian Glands Produces Pseudohypoaldosteronism 1-Like Ocular Disease in Mice. Am J Pathol 188:95-110
Muhlebach, Marianne S; Hatch, Joseph E; Einarsson, Gisli G et al. (2018) Anaerobic bacteria cultured from cystic fibrosis airways correlate to milder disease: a multisite study. Eur Respir J 52:
Livraghi-Butrico, Alessandra; Wilkinson, Kristen J; Volmer, Allison S et al. (2018) Lung disease phenotypes caused by overexpression of combinations of ?-, ?-, and ?-subunits of the epithelial sodium channel in mouse airways. Am J Physiol Lung Cell Mol Physiol 314:L318-L331
Chen, Gang; Volmer, Allison S; Wilkinson, Kristen J et al. (2018) Role of Spdef in the Regulation of Muc5b Expression in the Airways of Naive and Mucoobstructed Mice. Am J Respir Cell Mol Biol 59:383-396
Bennett, William D; Zeman, Kirby L; Laube, Beth L et al. (2018) Homogeneity of Aerosol Deposition and Mucociliary Clearance are Improved Following Ivacaftor Treatment in Cystic Fibrosis. J Aerosol Med Pulm Drug Deliv 31:204-211
Ge, Ting; Grest, Gary S; Rubinstein, Michael (2018) Nanorheology of Entangled Polymer Melts. Phys Rev Lett 120:057801
Reighard, Katelyn P; Ehre, Camille; Rushton, Zachary L et al. (2017) Role of Nitric Oxide-Releasing Chitosan Oligosaccharides on Mucus Viscoelasticity. ACS Biomater Sci Eng 3:1017-1026
Zhou, Jinsheng; Wang, Yanqian; Menard, Laurent D et al. (2017) Enhanced nanochannel translocation and localization of genomic DNA molecules using three-dimensional nanofunnels. Nat Commun 8:807
Livraghi-Butrico, A; Grubb, B R; Wilkinson, K J et al. (2017) Contribution of mucus concentration and secreted mucins Muc5ac and Muc5b to the pathogenesis of muco-obstructive lung disease. Mucosal Immunol 10:829

Showing the most recent 10 out of 76 publications